Y Hpc TP. H o Chi Minh * Tap 20 * So 6 * 2016 N g h i e n cmi Y hpc
KHAO SAT TAC DUNG KHANG VIEM VA SU* THAY D 6 I NIEM MAC DA DAY CHUOT NHAT TRANG KHI KET HOP CHE PHAM
D O C H O A T TANG KY SINH (DU-HUO-DANG-JI-SHENG) VA MELOXICAM TREN THl/C NGHIEM
DuongNggc Bdo*, Nguyen Thi Scm*, Nguyen Phuong Dung*
TOMTAT
Mfic tieu nghien cOu: Xu huong kil hop Dong Toy y Hong dieu tri ngdy cdng tdng, ddc biet Hong cdc binh ly ca xuang kh&p. Trong do sit kii hgp pho biih nhdi Id hdi thuoc Ddc hoqt tang ky sinh (DHTKS) vd Meloxicam.
Nhdm khaj sdt tdc dung tdc dung Midng viim vd su thay doi Hin dq ddy khi phdi hgp hai chi'phdm ndy, chung tdi dd tiBi harih thuc hiin de tdi "Khdo sdt tdc dung Ididng viim vd su thay doi niim mqc da ddy diugt nhdt Hang khi Mi hgp che pham Ddc hoqt tang ky sinh (Du-huo-dang-ji-shmg) vd meloxicam Hin thuc nghiim ".
Phuong phdp nghien ciiu: Thuc hiin hai md hinh gdy viim: Gdy phu chan chugt bang carrageenan vd gay u hgt thuc nghiem bang cdch cmf viin bong cotton. Cum md hirdi cdy u hat, ddnh gid su thay dm niim mqc dq day chugt nlmt Hdng.
Kei qua: Sie fcei hgp chephmn E)dc hoqt tang ky sinh vd meloxicam deu co tdc dung khdng viem tdi. Ket hop Ddc hoqt tang ky sinh (uohg lieu 1,818 g bgt thuoc/kg diugt) vai meloxicam (udng lieu 8 mg/kg diugt) Ididng ldm tSng hiiu qud khdng viim so vdi khi diing ning mdi thud'c nhung ldm tang chi sd'loet dq ddy. Kil hgp Dgc hoqt tang ky sinh (uong lieu 1,818 g bgt thuoc/kg diugt) vai meloxicam (udng liiu 4 mg/kg chugt) co hieu qud Idtdng viim tucmg ducmg khi diing rieng meloxicam 8 mg/kg, hoac Ddc hoqt thang ky dnh 1,818 g bdt thud'c/kg vd ldm gidm chi so loet dq day. Kit hgp Ddc hoqt tang ky sinh (ud'ng lieu 0,909 g b6t thud'c/kg chuot) vcn meloxicam (umg liiu 4mg/kg chugt) co hiiu qud khdng viem tucmg duang khi diing rieng Htng thud'c hodc phdi hgp (meloxicam 8 mg/kg, Dgc hoqt tang ky sinh 1,818 g bdt thud'c/kg) vd ldm gidm chi so loet dq ddy.
Kit ludn: Su fcei hgp meloxicam 8 mg/kg v&i Ddc hoqt tang ky sinh co tdc dung Ididng viim tucmg dieong meloxicam 8 mg/kg vd ldm tdng (hi so lod dq ddy; su kei hgp meloxdam 4 mg/kg v&i Ddc hoqt tang ky sinh ldm tdng tdc dung khdng viim so v&i dung riing cdc thud'c vd gidm chi sd'loet dq ddy chudt nhdt.
Tit khoa: Khdng viim, Dgc hoqt tang ky sinh, meloxicam, dq ddy.
ABSTRACT
EXPERIMENTAL STUDY ON ANTI-INFLAMMATORY EFFECT AND VARLMTONIN THE STOMACH OF MICE WHEN COMBINING DU-HUO-DANG-JI-SHENG TABLETS AND
MELOXICAM.
Duong Ngoc Bao, Nguyen TM Son, Nguyen Phuong Dung
* Y Hoc TP. Ho CM Minh * Vol. 20 - No 6 - 2016:75 - 85 Objectives: Tendency combining Eastern and Western medidne in Heatment is increasing, parHcularly in musculoskeldal pathologies. In which the most popular combination is combined Du-huo-dang-ji-shmg with Meloxicam. The study was performed to clarify anH-inftammatory effects and variation in the stomach of mice whm combiningDu-huo-dang-ji-sheng tablets and meloxicam".
Methods: Edema was by carrageman and granuloma was inducted by cotton, aceHc add-induced acute
* Khoa Y hoc co truyen- D^i hoc Y DUQC Tp. Ho Chi Minh
Tdc gid liSn lac. ThS.BS. Duong Ngpc Bao DT: 01267336917 Email: [email protected] 75
N g h i e n cmi Y hpc Y Hpc TP. H S Chi M i n h * T a p 20 * So 6 * 2016 abdominal torithing pain on mice, hot-plate test. In the end of granuloma transplanHng, evduate the gastric mucosal changes and the number of platelets in mice
Results- The combinaHan between Du-huo-dang-ji-sheng and meloxicam has good anH-inftammatory effect The combinaHon betiveen Du-huo-dang-ji-sheng (1.818 g dose of powder/kg mice) and meloxicam (8 mg/kg mice) did not increase the anH-inftammatory effect than used separately but increased the index of gastric ulcers; The combinaHon betivem Du-huo-dang-ji-sheng (1.818 g dose of powder/kg mice) and meloxicam (4 mg/kg mice) have anti-inftammatory effed equivalent to meloxicam 8 mg/kg, or Du-huo-dang-ji-sheng 1.818 g powder/kg, and reduced index of gastric ulcers; The combination between Du-huo-dang-ji-sheng (0.909 g dose ofpawder/kg mice) and meloxicam (4 mg/kg mice) have anti-inflammdory effect equivalent to use separately or in combination (meloxicam 8 mg/kg, Du-huo-dang-ji-sheng 1.818 g powder/kg), and reduced index of gastric ulcers.
Conclusions: The combinaHon between meloxicam (8 mg/kg mice) and Du-huo-dang-ji-sheng has anti- inflammatory effect equivalmt to meloxicam 8 mg/kg and increases the index of gastric ulcers; the combination betwem meloxicam (4 mg/kg mice) and Du-huo-dang-ji-shmg increases the anH-inftammatory effed and decreases the index of gastric ulcers.
Keywords: anti-inflammatory, Du-huo-dang-ji-shmg, meloxicam, stomach.
D A T V A N D E
Cac NSAIDs da va dang mang lai Meu qua khang viem tot cho benh nhan. Tuy nMen, NSAIDs Cling gay nMeu he luy cho tim mach, ih$n, dac biet la nhirng tac dung bat lod tren he tieu hoa nhu loet, xuat huyet tieu hoa, tieu ehay, tMeii mau, buon non, biaig an, dau bung i^' Vi the, tim kiem cac phuong each giam dau Meu qua, an toan cho benh nhan can dfeu tri bang NSAIDs luon la van de duoc quan tam.
Xu huong ket hop Dong Tay y trong dfeu tri ngay cang tang, dae biet trong cac benh ly eo xuong khop. Ket hpp NSAIDs voi thuoc eo tmyen trong dieu tri benh Iy xuong khop eo mang lai Meu qua mong doi, cu the la tang tac dung khang viem han che tac dung phu cua NSAIDS hay khong? Cho d a i nay, chua co nM'eu bing chiing khoa hpc tra loi cho eau hoi nay.
Theo so li^u thong ke ciia Benh vien Y hpc co truyen TP. HS CM Minh (2014-2015), cae che pham tir bai Dpc hoat tang ky sinh (DHTKS) va meloxicam c6 tan suat su dung eao nhat. Hai loai thuoc nay cung thuong dupe ket hpp trong dieu tri cac benh Iy xuong khop. Trong thanh phan cua Dpc hoat tang ky sinh co Cam thao. Bach thuoc. Que, Duong quy, day la nhi5ng vi thuoc CO tac dung chong loet da day (S) Co le vi the ma
cac thay Ihuoe phoi hpp bai thuoc Dgc hoat tang ky sinh voi meloxicam tren lam sang.
De gop phan tra loi cau hoi "Kei hgp Boc ho^t tang ky sinh voi Meloxicam co ldm tang hieu qud khdng viem vd ldm gidm tdc dung phu kich iing da ddy cua meloxicam khong?", trong pham vi ngMen cuu nay, chiing toi khao sat tac dung khang viem giiia che pham Dpc hoat tang ky sinh va meloxicam tren cac mo Mnh chugt nhat trang gay viem thuc ngMem.
M u c tieu n g h i e n c u u
Khao sat tac dung khang viem giiia die phain Dpc hoat tang 1^ sinh va meloxicam trsi thuc ngMem.
Muc tieu cu the
Khao sat tac dung khang viem cua che pham Dpc hoat tang ky sinh ket hpp meloxicam tren mo hinh ehupt nhat trang gay phii chan bing carrageenin va mo hinh tao u hat bang cotton.
Khao sat su thay doi niem mac da day cua chupt nhat trang kM sii dung ket hop Dpc hoat tang ky sinh voi meloxicam.
NGLfVENUEU-PFIlTONGPHAPNGHIENCUlJ N g u y e n lieu
Che phaun Dpc hoat tang ky sinh. Moi vien bao pMm chiia cao kho cac dupe lieu sau: Dpc 76
Y Hpc T P . H b C h i M i n h * T a p 20 * S 6 6 * 2016 N g h i e n c m i Y hpc ho?t 330 mg, Phong phong 330 mg. Tang ky sinh
330 mg, D6 trpng 330 mg, Nguu tat 330 mg, Tan giao 330 mg, Sinh dia 330 mg. Bach thupe 330 mg, Cam thao 330 mg.
Bpt kho ciia: Te tan 60 mg. Que nhuc 60 mg, Nhan sam 60 mg, EXrong quy 60 mg, Xuyen khung 30 mg.
Ta dupe vua dii 01 vien bao phim.
Tieu chuan: TCCS SDK:V731-H12-10
Dpng vat tM ngMem: Chupt nhat trang eung phai (due), nang 18-22 g, chiing Sidss albino do Vien Pasteur thanh pho Ho CM Minh cung cap.
Bong cotton, carrageenan (Sigma Ltd Co., USA).
Dung dieh chong tham Omano imbidente (Ugo B2isile, Italia). Meloxicam (Meloxicam 7,5 mg - Stada®).
Phirong p h a p n g h i e n dm Mo hinhgay viem gdy hang carrageenan.
Theo phuang phap Winter -1962 '^•^
Do the tich chan chupt binh thuang (Vo) tren may Plethysmometer. Nhiing chan phai ciia ehupt vao dung dich chong tham den khuyu chan, nhan giii ban dap de co dinh, gM nhan fhe tich tren may, tieh hanh do 3 ^ va lay ket qua trung binh.
Chupt duoc gay viem bang each tiem duoi da gan ban chan phai 0,05 ml hon hop dung dich carrageenan 1% (h6n hpp dung dich carrageenan 1% pha trong dung dich nuoc muoi sinh Iy 0,9% dupe chuan bi truoc kM thu ngMem 2 gia de carrageenan truong no). Chupt sau kM gay viem dupe cho vao long co gia do de tranh nMem trimg chan.
Sau kM tiem 3 gio, do the tich chan chupt (V3h) tren may Plethysmometer. Cac chupt co chan sung phii tren 50% so voi binh thucmg dupe chpn cho tM ngMem va dupe chia ngau nMen vao cac 16, chupt duac chia 8 16. Chupt trong moi 16 duoc cho uong nuoc hoac thuoc dmg the tich 0,1 ml/10 g the trpng:
- Lo 1 (n=10): Uong nuoc cat (Chiing)
- Lo 2 (n=10): Uong Meloxicam, lieu 8 mg/kg the trpng (Melo 8)
- Lo 3 (n=13): Uong Meloxicam, heu 4 mg/kg (he trpng (Melo 4)
- Lo 4 (n=10): Uong che pham DHTKS 1/10 Dmax, tuang duong 1,818 g bpt thud'c/kg chupt (DHTKS 1,818)
- Lo 5 (n=ll): Uong che pham DHTKS 1/20 Dmax, tuong duong 0,909 g bot thu6c/kg chuot (DHTKS 0,909)
- Lo 6 (n=7): Uong che pham DHTKS (lieu 1/10 Dmax) va dung dieh meloxicam 8 mg/kg the trpng (Melo 8 + DHTSK 1,818)
- Lo 7 (n=13): Uong che pham DHTKS (lieu 1/10 Dmax) va meloxicam h'eu 4 mg/kg (Melo 4 + DHTSK 1,818)
- Lo 8 (n-13): Uong ehe phaim DHTKS (lieu 1/20 Dmax) va meloxicam lieu 4 mg/kg (Melo 4 + DHTSK 0,909)
Cho chupt UOTig thuoc trong 6 ngay tiep theo ciia thii ngMem va do (he tich chan moi ngay, thoi diem do liic 9 gia sang. Ky Meu the tidh chan chupt theo ngay: VI, V2, V3, V4, V5, V6.
Danh gia ket qua:
Tac dung khang viem dupe danh gia bang ty Ie % miic dp giam the tieh sung phu ciia 16 thii ngMem so vol 16 chiing.
Miic dp phii chan chupt dupe tinh theo c6ng thiic:
Vt-Vo
X= xlO0%
Vo Trong do.
X- Do phu tinh theo %
Vo: Thi'tich dian chuot tneac khi gay viem.
Vt: ThS tich dian chuot a then diem t sau khi gay viem.
Tac dung khang viem ciia thuoc dupe danh gia bang kha nang lie che phan iing phii (%) dupe bieu thi bang ty le % giam miic d6 tang the tich ban chan chupt 6 cac 16 doi chiing va 16 thii
Nghien cufu Y hpc Y Hpc TP. Hb Chi M i n h * Tap 20 * Sb 6 * 2016 so voi miic dp tang ciia 16 khong uong thuoc,
dupe tinh theo eong thiic:
1% = (AVe % -AVt %)/ AVc %
Trong do. AVc %; Trung Unh do tdng thetich chan chugt cf Id khang dihi tri
AVt %: Tmng bmh do tang thetich chan chuot a Id umg thuoc.
Md hinh gdy u hgt thuc nghiem bang cdy vien bong cotton.
Mpt miu cotton co trpng lupng 10 + 2 mg dupe ve tron va say tiet khuan trong 2 gia o nMet dp 1 2 0 ^ trong tu say. Chupt dupe gay me bang ether, cao sach long vimg lung phia tren, dimg keo phau thuat mat bam mpt 16 chech sang ben, luon keo vao huong tren ^ u , mo rpng 2 miii keo de tach ky da Iimg ra khoi co, rbi cay vien cotton duoi da. Khau bang cM v6 trung de noi lien ch6 mo 6 lung t^*-
Mo chugt bang dung cu da dupe tiet khuan bang each ngam trong eon 90%. Sat trimg vet mo bang dung dieh con iod (Povidine).
Chupt trong m6i 16 dupe eho uong nuoc hoac thubc cung the tich 0,1 ml/lOg the trgng:
- L6 1 (n=12): U&ig nuoc cat (Chiing) - L6 2 (n=12): Uong meloxicam, h'eu 8 mg/kg the trpng (Melo 8)
- Lo 3 (n=12): Ubng meloxicam, lieu 4 mg/kg the trpng (Melo 4)
- Lo 4 (n=12): Ubng che pham DHTKS 1/10 Dmax, tuong duong 1,818 g bpt thuoc/kg chupt (DHTKS 1,818)
- Lb 5 (n=10): Ubng che pham DHTKS 1/20 Dmax, tucmg duong 0,909 g bpt thubc/kg chupt (DHTKS 0,909)
- Lo 6 (n=ll): Ubng che pham DHTKS (lieu 1/10 Dmax) va dung dich meloxicam 8 mg/kg the trpng (Melo 8 + DHTSK 1,818)
- Lo 7 (n=ll): Ubng ehe ph&n DHTKS (Ueu 1/10 Dmax) va meloxicam lieu 4 mg/kg (Melo 4 + DHTSK 1,818)
- Lo 8 (n-10): Ubng che pham DHTKS (heu 1^0 Dmax) va meloxicam lieu 4 mg/kg (Melo 4 +
DHTSK 0,909)
Cho chupt ubng trong 7 ngay, moi ngay mot lan vao mgt gio nhat dinh voi the tich 0,1 ml/10 g trpng lupng chubt. D&i ngay thii 8, giet chet ehupt, boc tach u hat, can tuoi ngay timg u hat Sau do cho u hat vao tii say 6 60 ^ trong 18 gio, can timg u hat kho.
Thong sb danh gia
Khbi lugng u hat tuoi/ kho ciia timg chuot (Sau kM da trit khbi lupng truoc kM cay).
Ty le % do giam khoi lupng u hat ciia 16 tiiii so voi 16 chiing bieu tM bang eong thiie sau:
X % = [(Md, - M*) / Mdi] X100
X %: Ty le % gidm khdt lugng u hat cita Id thie so vm 16 chdng.
Mdi: Khoi lugng u hat trung binh cua 16 chung.
Ma,- Khoi lumtg u hat trung binh cua Id thie.
Danh gia su thay doi niem m^c da day chupt nhat trang
Cubi m6 hinh u hat (ngay Ihii 8) giet chupt bang da CO2, nia da day chugt nhat trong nuoc muoi sinh ly, quan sat niem mgc da day chupt bang kinh M&i vi soi noi, bng kinh 10. CM so loet dupe gM nhan theo thang di&n ciia Takagi va Okabe de danh gia miic dp tbn thuong da day P>;
0 = Khong CO tbn thuong 1 = Hiii ne ruem mac va xuat huyet 2 = 1-5 tbn thuong nho (1-2 mm) 3 = NMeu hon nam tbn thuong nho hoac mot tbn thuong trung gian (3-4 mm)
4 = Hai den tbn thirong trung gian nMeu hon hoac mpt ton thirong ggp (> 4 mm)
5 = Loet thiing.
Trong do, cM sb loet 5 duge tinh la miic do tbn thuong da day 100%.
Xit ly ket qud
Cac d u lieu duac trinh bay duoi dang Mean ± SEM (standard error of mean - sai so chuan ciia sb trung binh) .Viec xii Iy thong ke trong de tai nay dimg phan mem STATA 13.0.
Su khac biet gitia cac 16 dupe phan tich bing 78
Y Hpc TP. Hb Chi M i n h * Tap 20 * Sb 6 * 2016 Nghien cmi Y hpc phuong phap Wilcoxon, Mann - Whitney - U
test. P < 0,05 dupe cho la eo y nghia thbng ke.
KETQUA
Ket qua mo hinh gay viem bang tac nhan carrageenin
Ket qua su thay dbi dp phii chan diupt theo then gian giua cac 16 dupe trinh bay a bang 1 va bang 2.
Bang LSw thay do: do phii chan (%
STT 1 2
3
4
F,
6 L6 Chijng (n=10) Melo 8 (n=10) BUTKS 1,818 (n=10) MoloS+BHTKS
1,818 (n=7)
Melo4(n=13)
Melo4 + BHTKS 1,818 (n=13)
Thai gian Bo phCi (%) B6ph£l(%)P2.,
% GPSVC BophCl(%) P3-1
% GPSVC Do phu (%)
P «
% GPSVC Do phii (%)
% GPSVC Bo phu (%) Pm P M
% GPSVC
cita cdc Id chupt uon^
Sgio- 121,2±
23,84 113,7
±29,15 121,28 ±
49,8 113,52 ±
21,6 105.8±
21,46
102 ±43,63 Ngasri 107,46
±26,67 71,57 ± 26,7"
33,4 81,17±
37,04- 24,46 69,07 ±
9,6*
35,72 90,74±
21.24 15,66 59,71±
26,35
#
44,44
DHTKS 1,818 g bgt Ngay 2
86,99
±29,17 47,51±
20,03"
45,38 61,64±
25,06*
29,14 51,83±
11,83*
40,42 78,29±
16,42 10 45,43±
25,16
#
47,76 Ngay 3 73,42±
26,97 31,01±
18,63*
57,76 47,8 ± 21,13*
34.9 35,25±
13,44*
51.99 67.71±
17.51 7,78 34.87±
19,16 m 52,51
thuoc/kg kei hpp vdi melpxtcam.
Ngdy 4 63,89±
15,53 20,46±
13,54"
67,98 36,21±
19.98"
43,32 26,65 ±
14,7*
58.29 59.76±
15.14 6,46 26,89±
15,03 m 57,91
Ngay 5 52,4 ±9.86 12.58 ±9,5"
75,99 23,01 ±
15,9"
56.09 11.73 ±7,36
77,61 Ngay 6 36.83 ±8.3
6 ±6.07"
83,7 11,08±
8.44"
69,91 4,72 ± 2,91*
87,18 52,27± 13,57 42,6 ±9,17
0.25 16,11± 10,04
m 69,26
-0,15 10,21±
10,34 m 72,28
% GPSVC. Ty le % ^dm phit sau viem c^.
(*) P<0,05. Co y nghia thong ki so v&i 16 chieng, do tin cay 95 %.
(**) P<0,01: Co y nghia thohgkiso v&i Id diieng, id tm cay 99 %.
(S) P<0,05: Co y nghia Ih&hg ke so v&i 16 meloxicam 4 mg/kg, d6 tin cdy 95 %.
(SK) P<0,01. Co y nghia thong ke so v&i Id meloxicam 4 mg/kg, do tin cay 99 % L6 chiing: Dp phii chan chuot sau 3 gio tiem
carrageenin la 121,2%, sau do giam dan d a i ngay thii 6 con 36,83%.
Lb chupt ubng Melo 8 do phii giam co y ngMa thcttig ke so vol 16 chiing. Sau 1 ngay, dp phii giam con 71,57%, sau do giam dan va cM con 6% vao ngay thii 6.
L6 ubng DHTKS 1,818 va DHTKS 0,909 co dp phii giam eo y ngMa thbng ke so vai 16 chiing. Sau 1 ngay dp phii giam con 81,17% va 55,08%, sau do giam dan va cM eon 11,08% va 14,06% vao ngay thii 6. Su khae biet giua hai !6
ubng DHTKS kh6ng co y nghia thong ke (P<0,05).
Lo ket hgp Melo 8 + DHTKS 1,818: Do phu giam CO y ngMa thbng ke so vol 16 chiing (P<0,05). Sau 1 ngay dp phii giam con 69,07% sau do giam dan va cM eon 4,72% vao ngay thii 6.
Mac dii su ket hpp meloxicam voi DHTKS co lam tang miic dp giam phii so vai kM dimg rieng timg thuoc, nhung su khac biet nay khong co y ngMa thbng ke (P4-2, P4-3> 0,05).
Lo chupt ubng Melo 4: Dp phu giam 15,56%
(sau 1 ngay dimg fliuoc), khac biet khong co y ngMa thbng ke so voi 16 chiing (P>0,05). Nhu
Nghien curu Y hpc Y Hpc TP. Hb Chi M i n h * Tap 20 * S b 6 * 2016 vay, kM giam lieu 50%, meloxicam kh6ng con tac
dung khang viem tren chugt nhat trang.
Lo chugt ubng Melo 4 + DHTKS 1,818: Do phii giam CO y nghia thong ke so voi 16 chiing (P<0,05). Sau 1 ngay do phu giam con 59,71%, sau do giam dan va cM con 10,21% vao ngay thii 6. Mac dii h'eu meloxicam da giam 50%
(meloxicam 4 mg/kg), nhung Meu qua giam phii ciia 16 ket hgp (Melo 4 + DHTSK 1,818) trong 6 ngay vSn tucmg duong voi dimg thuoc rieng re Bdng 2.Sie thay doi do phd chan (%>) cua cdc Id chugt u
(Melo 8, DHTKS 1,818) va ca 16 ket hgp Melo 8 + DHTKS 1,818(P6-5<0,01).
Ket hgp Melo 8 + DHTKS 1,818 khong I ^ tang tac dung khang viem tren chugt nhat trang so vol kM sii dung rieng re timg loai thuoc.
Ket hgp Melo 4 + DHIKS 1,818 tao dugc tac dung khang viem tuang duong kM dimg rieng Melo 8 hoac DHTKS 1,818.
g DHTKS 0,909 g bdt thud'c/kg vd meloxicam.
STT 1 2
3
4
5 Lo Chung (n=10) Melo 8 (n=10) Melo 4 (n=13) DHTKS 0,909 (n=11) Melo 4 + BHTKS 0,909 (n=13)
Thin gian BO Phil (%) BSphii(%) P2-1
% GPSVC Bo phii {%)
% GPSVC DQphu(%)
P«
% GPSVC Bophil(%)
Pn P M
% GPSVC 3 g i * 121.2 ±23.84 113.7 ±29.15 106.87
±21.45 91.1 ±29,53
94,47 ±18,87 NgSy1 107,46
±26,67 71,57±
26,7"
33,4 90.74±21.24
15.56 . 55.08±
20.47"
48.74 62.87± 12,1
m 41,49
Ngay 2 86,99 ±29,17
47,51
±20,03"
46,38 78,29± 16,42
10 39.75±21,64'
54,3 47 ±10
m 45,97
Ngiy 3 73.42 ±25.97 31,01 ±18,53*
57.76 67.71 ±17,51
7,78 30,71 ±17,04'
58,17 38,36± 13,07
m 47,75
Ngiy 4 63,89 ±15,53
20,46±
13,54"
67,98 59,76± 15,14
6.46 26 ±17.81*
59.31 25,65±9,94
m 59,85
Ngiy 5 52,4 ±9,86 12,58±9,6"
76,99 52,27± 13.57
0.25 17,38±
12.53- 66,83 17.44±7.33
66,18 Ngiy 6 36.63 ±8.3
6 ±6.07"
837 42,6 ±9,17
-0.15 14.06±11,e7
61.82 6.86 ±8,03
##
81,37 Ghi chu-
% GPSVC: Ty le % ^im phii sau vthn cap.
(*) P<0,05: Co y nghia thdng ki so -D&i Id chimg, do tin cay 95 %.
(**) P<0,01: Co ^ nghia thdng ke so v&i 16 chieng, do tin cay 99 %.
(W P<0,01: CO y nghia thdng ki so v&i Id meloxicam 4 mg/kg, dd tin cay 99 %.
L6 chupt ubng Melo 4 + DHTKS 0,909 co dp phii giam co y ngMa thbng ke sp voi 16 chiing (P<0,05). Sau 1 ngay dp phii giam con 62,87% sau do giam dan va dhi con 6,86% vao ngay thii 6.
Mac du Ueu meloxicam da giam 50% (meloxicam 4 mg/kg), nhimg Meu qua giam phii eiia 16 ket hgp (Melo 4 + DHTSK 0,909) trong 6 ngay van tuong duong voi dimg thubc rieng re (Melo8, DHTKS 0,909) (P5-3<0,01).
Viec ket hpp Melo 4 + DHTKS 0,909 cho tac dung khang viem tuong duong Melo 8, dong thoi tac dung khang viem tang so voi kM dung rieng DHTKS 0,909.
Ket hpp meloxicam 8 mg/kg va DHTKS 1,818 g bpt thubc/kg khbng lam tang tae dung khang viem so v6i dimg rieng cac thuoc.
Ket hgp meloxicam 4 mg/kg va DHTKS 1,818 g bpt thubc/kg lam tang tac dung khang viem so voi dimg rieng DHTKS 1,818 g bpt thuoc/kg va meloxicam 4 mg/kg va tuong duong meloxicam 8 mg/kg.
Ket hgp meloxicam 4 mg/kg va DHTKS 0,909 g bgt thubc/kg lam tang tac dung khang viem so voi dimg rieng DHTKS 0,909 g bgt fliubc/kg va meloxicam 4 mg/kg va tuong duong meloxicam 8 mg/kg.
Y Hpc TP. Hb Chi M i n h * Tap 20 * Sb 6 * 2016 Nghien ctru Y hoc Ket qua gay u hat thirc nghiem bang each
cay vien bong cotton
Tdc dyng khdng viem cua DHTKS 1,818 g bot thuoc/kg kit hgrp vdi meloxicam
Bdng 3 . Khoi lugng u hat Heai giiia cdc Id chudt udng DHTKS 1,818 g hot thudc/kg kii hop v&i meloxicam Ket qua so sanh khoi lugng u hat tuoi, u hat khb giua cae 16 dugc trinh bay a Bang 3 va Bang 4.
S I I 1 2 3 4 5 6
L6 Chu'ng Melo 8 DHTKS 1,818 Melo8 + DHTKS1,818
Melo4 Melo4 + DHTKS1,818
n 12 12 12 11 12 11
Khdi luong u hat tvoi (q) 55,89 ±5.8 41 ±4.83"
41.17±5.44"
45.81 ±7*
50.74 ±12.1 42.1 ± 4 . 4 1 "
IUi>c giam khdi luong u hat tuoi s o voi chiing (%) 26.64"
26,35- 18,04*
9,21 24.68*
(*) P<0,05: Co y nghia thmg keso vdi Id chmig, do tin cdy 95 %.
(**) P<0,01. Co y nghia thmg ke so v&i Id chieng, dd tin cay 99 % L6 ehiing: Khbi lugng u hat tuoi sau cay 7 ngay la 55,89 g.
Lb chugt uong Melo 8: Khbi lupng u hat tuoi la 41 g, giam co y ngMa thong ke so v6i 16 chiing (P<0,01). 0 1 6 nay ciing co su giam khoi lugng u hat tuoi so vdi chiing eao nhat trong cac 16 (26,64
%).
L6 chugt ubng DHTKS 1,818 va DHTKS 0,909: Khbi lugng u hat tuoi (an luprt la 41,17 g va 45,98 g, giam co y ngMa thong ke so voi 16 chiing (P<0,01 va P<0,05). Kh6ng khac biet co y nghia thbng ke giiia 2 lb nay va so voi 16 ubng meloxicam 8 mg/kg (P>0,05).
L6 Melo 8 + DHTKS 1,818: Khoi lupng u hat tucri la 45,81 g, giam co y ngMa thbng ke so vod 16 chiing (P<0,05).
Lb Melo 4: Khoi lugng u hat tuoi la 50,74 g.
(P>0,05). Nhu vay, kM giam heu 50 %, meloxicam khong eon tae dung khang viem man tren chupt nhat trang.
L6 Melo 4 + DHTKS 1,818: Khoi lupng u hat tuoi la 42,1 g, giam eo y nghia thong ke so vdi 16 chiing (P<0,05). Mac dii lieu meloxicam da giam 50% (meloxicam 4 mg/kg^, nhung khoi lupng u hat tuoi van tuong duong vdi lb dimg thu6c rieng re (Melo8, DHTKS 1,818) va ca 16 ket hpp Melo 8 + DHIKS 1,818 (P>0,05).
Trong thii ngMem tac dung khang viem man, 16 chupt uong Melo 8 co khbi lupng u hat tuoi thap nhat va % miic gjam khoi lugng u hat tuoi so vdi chiing cao nhat (26,64%), Hep theo la 16 chugt ubng DHTKS 1,818 va Melo 4 + DHTKS 1,818 (26,35%; 24,68%). Tuy nMen, su khac biet giiia cae 16 nay kh6ng cd y nghia thong ke (I>>0,05).
khac biet kh6ng y nghia thraig ke so vdi 16 chiing
Bdng 4. Khoi lugng u hat kho giiea cdc Id chudt uohg DHTKS 1,818 g bdt thud'c/kg kii hap vai meloxicam STT
1 2 3 4 5 6
L6 Chung Melo 8 DHTKS 1,818 Melo 8 H-DHTKS 1,818
Melo 4 Melo4 + DHTKS1,818
n 12 12 12 11 12 11
Khdi l u ' ^ g u hat kho (g) 6.05 ±1.07 3.66 ±0,89"
3,51 ±0,89"
4,63 ±0,94*
5,91 ±3,02 4,64 ±0,75*
Min; giam khdi iif^ng u hat khd so vdi chinig (%) 39,59
42,01 23,47 2,34 23,23 (*) P<0,05: Co y nghia th&ig ki so v&i Id chimg, do tin cay 95 %.
(**)P<0,01: Coy nghia tiiSngkiso v&i Id chung, do tin cay 99 %.
L6 chiing: Khoi lugng u hat khd la 6,05 g.
N g h i e n cmt Y hpc Y Hoc TP. H b Chi M i n h * T a p 20 • So 6 * 2016 Lo chuot uong Melo 8: Khoi lumig u hat kho
la 3,65 g, giam co y nghia thong ke so voi 16 chiing (P<0,01).
Lo chuot uong DHTKS l,818va DHIKS 0,909: Khoi luong u hat kho Bn luot la 3,51 g va 4,54 g, giam co y nghia thong ke so voi 16 chiing (P<0,01 va P<0,05). Khong co su khac biet thong ke ve khoi Imjng u hjt kh6 giiia 2 16 nay (E>0,05).
Lo Melo 8 + DHTKS 1,818: Khoi luong u hat kho la 4,63 g, giam co y nghia thong ke so voi 16 chiing (PO,05). Mac dii su ket hop nay giam khoi luong u hat kh6 it hem so vol dimg rieng tung thuoc nhung su khac biet nay khong co y nghia thong ke(P> 0,05).
L6 Melo 4: Kh6i luong u hat kho la 5,91 g, khac biet kh6ng co y nghia thong ke so voi 16 chiing (P>0,05). Nhu vay, khi giam lieu 50 %, meloxicam khong con tac dung khang viem man tren chuot nhat trang.
Lo Melo 4 + DHTKS 1,818: Khoi luong u hjt kho la 4,64 g, giam co y nghia thong ke so voi 16 chiing (P<0,05). Mac dii lieu meloxicam da giam 50 % (meloxicam 4 mg/kg), nhung hieu qua giam khoi lugng u hat kh6 van tuong duong so voi 16 dung thuoc rieng re (Melo 8, DHTKS 1,818) vk ci 16 Melo 8 + DHTKS 1,818 (P> 0,05).
Ket qua bang 3 va bang 4 cho tfiay viec ket hop Melo 8 + DHTKS 1,818 khong lam tang tie dung khang viem man. Trong khi do, viec ket hop meloxicam (4 mg/kg) vol DHTKS (1,818 g/kg) cho hieu qua khang viem man tot hon (so vol Melo 4), tuong duong vol 16 phoi hap Melo8 + DHTKS 1,818.
Tie dung khang mem ciia DHTKS 0,909 g Mt thuoc/kg kei hap vai meloxictmi,
Ket qua so sanh khoi lugng u hat tuoi, u hat kh6 giiia cac 16 duoc trinh bay 6 Bang 5 va Bang 6.
Ban STT 1 2 3 4 5
g5. Khm lupng u hat tuoi giUa cdc 16 diupt u6ng DHTKS 0,909 g bdt thud'c/kg ket hpp vdi meloxicam L6
Chiing Melo 8 Melo 4 BHTKS 0,909 Melo 4+DHTKS 0,909
n 12 12 12 10 10
Khdi iu^ng u hat tutxi (g) 55,89 ±5,8 41 ± 4 , 8 3 "
50,74 ±12,1 46,98 ±6,8*
47,04 ±6,65*
Mi>c giam khdi lirg'ng u hat tuoi so vdi chung (%) 26,64"
9.21 17,73*
15,84*
(*) P<0,05: Co y nghia thong kesovdilS chiing, d6 tin cay 95 %.
(**) P<0,01: Co ^ nghia thmg ke so vdi Id chimg, do tin cay 99 %.
L6 Melo 4 + DHTKS 0,909: Khoi lugng u hat khoi luong u hat tooi gan hrong duong so voi Moi la 47,04 g, giam cdy ngMa Ihong keso vdi 16 dimg thuoc rieng re (Melo 8, DHTKS 0,909) chiing (P<0,05). Mae dii lieu meloxicam da giam (R>0,05).
50% (meloxicam 4 mg/kg), nhung Meu qua giam STT
1 2 3 4 5
L6 Chijng Melo 8 Melo 4 DHTKS 0,909 Melo 4 +DHTKS 0,909
n 12 12 12 10 10
Kh6i luong u hat khd (g) 6,05 ±1,07 3,65 ±0,89"
5,91 ±3,02 4.54 ±1.17*
4,72 ±0.75*
Miic gidm khdi luvng u hat khd so vdi chiing (%) 39,59"
2,34 24,96*
21,98*
(*) P<0,05: Co i) nghia thdkg ke so vdi 16 chimg, dd tin cay 95 %.
(**} P<O,01: Co 1/ ngtua thmg he so v&i Id chimg, do tin cay 99 %.
Lo Melo 4 + DHTKS 0,909: Khoi lugng u hat chiing (P<0,05). Mac du lieu meloxicam da giam kho la 4,72 g, giam co y nghia thong ke so voi 16 50% (Melo 4), nhung hieu qui giam khoi luong
82
Y Hpc TP. Hh Chi Minh * T^p 20 * S^ 6 * 2016 Nghien cihi Y hpc u hat kh6 gan tuong duong so vdi dimg thuoc
rieng re (Melo 8, DHTKS 0,909) (P>0,05).
Tu ket qua bang 5 va bang 6 cho thay viec ket hpp Melo 4 + DHTKS 0,909 cho tac dung khdng viem mqn tuang dimng Melo 8.
Su ket hpp meloxicam 8 mg/kg va DHTKS 1,818 g bpt thuoc/kg khdng Iam tang Meu lue khang viem man.
Ket hgp meloxicam 4 mg/kg va DHTKS 1,818 g bgt (hu6c/kg ldm tdng tdc dung khdng viem mqn so vdi dimg rieng meloxicam 4 mg/kg va tuong duong meloxicam 8 mg/kg.
Ket hpp meloxicam 4 mg/kg va DHTKS 0,909 g bpt thuoc/kg ldm tdng tdc dung khdng viim mqn so vdi dimg rieng meloxicam 4 mg/kg va tuong duong meloxicam 8 mg/kg.
Su thay doi niem mac da day chupt nhat trang sau uong meloxicam va Dpc ho^t tang kysinh
Bdng 7. Miec do tm thucmg niim mqc dq ddy chudt nhdt Hang giUa cdc Id sau udng 7 ngdy (fheo thang dimi Takagi vd Okdbe, 1968)
L6 Chiing Melo 8 Melo 4 DHTKS 1,818 OhfTKS 0,909 Melo 8+DHTKS
1,818 Melo 4 +DHTKS
1,818 Melo 4 +DHTKS
0,909
S6 c h u ^ (n)
7 7 7 7 7 7 7 7
Diem 0 1,86 ±1,35*
0,71 ±0,95 1,71 ±1,13*
1,71 ±1,25*
2,57±1,61*
1.29 ±1.25 1.57 ±1.62
% tdn thuong niem mac
0 37,2 14,2 34,2 34,2 51,4 25,8 31,4 (*) P<0,05: Co y nghia thong ki so v&i 18 chiing, do tin cdy 95%.
L6 Melo 8 cd diem ton tiiuong raem mac da day chupt nhit la 1,86. KM giam niia lieu Melo 4 cd miic dg ton thuong da day thap nhat vdi 0,71 diem. Nhu vay, giam Vi Keu meloxicam cd y nghia gi^m ton thuong niem mac da day. Tuy nMen d Ueu 4 mg/kg nay khong ed tac dung khang viem, khdng cd tac dung giam dau.
Lo DHTKS 1,818 va DHTKS 0,909 cd diem ton thuong ni§m maic da day la 1,57 va 1,71, cae diem tdn thuong nay cd su khac biet ed y ngMa thdng ke so vdi 16 chiing (P<0,05). Ket qua nay phii hgp vdi tac dung phu dugc gjii trong mpt so che phsan DHTKS.
L6 Melo 8 + DHTKS 1,818 cd diem ton thuong niem mae da day chupt nhat la 2,57, tang cd y ngMa tiiong ke so vdi 16 chiing (P<0,05), cao nhat trong tat ca cac 16. Lo k^t hgp nay cd miic dp ton thuong da day cao hon so vdi dung rieng Melo 8 va DHTKS 1,818 nhung su khac biet giiia cac Id nay khdng cd y ngMa thong ke (P>0,05).
Lo Melo 4 + DHTKS 1,818 cd diem ton thuong mem mac dei day chugt nhat la 1,29, su khac Met nay khdng cd y ngMa thong ke so vdi Id ehiing (P>0,05). L6 ket hop nay cd miic dp ton thuang da day thap hon so vdi dimg rieng Melo 8, DHTKS 1,818 va eao hon so vdi Id Melo 4 nhung su khac biet giiia cae 16 nay khong co y ngMa tiiong ke (P>0,05).
L6 Melp 4 + DHTKS 0,909 co diSn tdn thuong Mem mac dg day chupt nhat la 1,57, su khae biet nay kh6ng cd y ngMa thong ke so vdi 16 chiing (P>0,05). Ld ket hpp nay cd miic do ton thuong da day thap hon so vdi dimg rieng Melo 8, DHTKS 0,909 va cao hon so vdi Id Melo 4 nhung su khac biet giua cac 16 nay kh6ng ed y ngMa thdng ke (P>0,05).
Vi?c ket hgp Melo 4 + DHTKS 1,818 va Melo 4 + DHTKS 0,909 giam miic do tdn thuong da day (1,29 diein; 1,57 diem) so vdi meloxicam 8 mg/kg va DHTKS 1,818 g bdt thudc/kg,
Viec ket hpp Melo 8 + DHTKS 1,818 lam tang tdn thuong ni^m mac da day chupt nhSt (51,4 %) so vdi dimg rieng DHTKS 1,818 g bpt thudc/kg va meloxicam 8 mg/kg.
Viec ket hgp Melo 4 + DHTKS 1,818 giam t6'n thuong mem mac da day chupt nhat (25,8 %) so vdi dung rieng DHTKS 1,818 g bdt thuoc/kg va meloxicam 8 mg/kg.
Vile ket hpp Melp 4 + DHTKS 0,909 giam tdn thuong mem mac dg day chudt nhat (31,4 %) so
83
Nghien cuu Y hgc Y Hpc TF. Hb Chi Minh * T^p 20 * So 6 * 2016 vdi dimg rieng DHTKS 0,909 g bpt thudc/kg va
meloxicam 8 mg/kg.
BANLUAN
Hieu qua khang viem khi k@t hpp meloxicam va dpc hoat tang ky sinh Kei qud thinghi$m cho thay
Tren m6 hinh gay phu chan chupt bang carrageenin, cac 16 phoi hgp: Melo 8 + DHTKS 1,818, Melo 4 + DHTKS 1,818, Melo 4 + DHTKS 0,909 deu ed tac dung khang viem khac biet cd y ngMa ihdng ke so vdi Id chiing (P<0,05) va tuong duong Melo 8. Dac biet cac Id ket hpp the Men Meu qua khang viem ro ret so vdi cac Id don ddc, trong do 16 Melo 8 + DHTKS 1,818 cd kha nang lie che viem cao hon Melo 8 d ngay 6 Ihe Men tae dvng Mep dong cpng. Lo Melo 4 khdng ed tac dimg khang viem, nhung kM phoi hgp vdi DHTKS 1,818 va DHTKS 0,909 cd tac dung khang viem the Men tac dung Mep dong tang miicDieu nay ggi y cho viee nen giam lieu meloxicam va DHTKS kM ket hpp.
Tr§n md hinh cay u hat (bdng cotton), cac 16 phdi hgp: Melo 8 + DHTKS 1,818, Melo 4 + DHTKS 1,818, Melo 4 + DHTKS 0,909 tang tac dyng khang viem man (lam giam trpng lupng khdi u hgt). Tac dung nay tucmg duong vdi 1 ^ Melo 8.
Nhu vay, DHTKS khi sii dung phdi hpp vdi meloxicam tang tac dung khang viem cap mgnro.
Anh huong c6a viec ket hgp meloxicam va dpc hoat tang ky sinh tren ni^m mac d^ day Kei qud thi nghim cho tha'y
So vdi cac Id sii dung don ddc Melo 8, cac 16 DHTKS 1,818, DHTKS 0,909 va dae biet la 16 phdi hgp Melo 8 + DHIXS 1,818 cd miic do ton thuong dg day khac biet ed y nghia tiidng ke so vdi chiing (P<0,05), con cac 16 phoi hgp DHTKS 1,818, DHTKS 0,909 va niia Heu meloxicam (4 mg/kg) CO miic dp ton thuong da day khong co y ngMa thdng ke so vdi 16 chiing (P>0,05). Dieu nay chiing td rang, viec phdi hgp va giam Vz heu
meloxicam lam giam tMeu miic do ton thuone da day so vdi dimg don dgc cae thuoc DHTKS va dimg nguyen lieu meloxicam 8 mg/kg khi phdi hgp.
Hieu qnk khang viem
Ket hgp DHTKS (udng Heu 1,818 g bgt thudc/kg chudt) vdi meloxicam (uong beu 8 mg/kg diupt) khdng lam tang Meu qua khang viem so vdi kM diing rieng m6i thudc (P>0,05);
Ket hgp DHTKS (u&ig H ^ 1,818 g bot ihudc/kg chugt) vdi meloxicam (uong lieu 4 mg/kg chudt) cd Meu qua khang viem tirong duong kM dimg rieng meloxicam 8 mg/kg hoaic DHTKS 1,818 g bpt tiiude/kg (P>0,05);
Ket hpp DHTKS (udng Heu 0,909 g bot thuoc/kg chupt) vdi meloxicam (uong lieu 4 mg/kg chudt) ed Meu qua khang viem tuong duong kM dimg rieng timg tiiuoc hoac phoi hop (meloxicam 8 mg/kg, DHTKS 1,818 g bot thudc/kg) (P>0,05).
S u thay doi niem mac da day
Ket hpp DHTKS (uraig Heu 1,818 g bot thudc/kg chupt) vdi meloxicam (uong Heu 8 mg/kg chugt) lam tang cM sd loet da day (0,71 va 0,86) so voi kM dimg rieng mdi thuoc (P>0,05);
Ket hgp DHTKS (udng Heu 1,818 g va 0,909 g bpt thudc/kg chugt) vdi meloxicam (uohg Heu 4 mg/kg chupt) lam giam cM sd loet da day (0,57 va 0,29) so vdi kM dimg rieng m6i fliuoc (P>0,05).
TAI UEU THAM KHAO
1 B9 Y te (2009). Benh hoc ca xmmg Oiap ndi Hnw. Nha xuSt bin giao dye Viet Nam, tr. 344-346.
2 P e m n e JW, BorUe L, Heydet E, Partridge R, Ross ¥K, Rmglerl (1959). Adienal corticoid activities of 9a-fluoro-lie, 16a, 17a 21- tetcahydioxy-1, 4-pregnadiene-3,20-dione-lA'.
Endtxrinohgy, 6^3) ^7-U7.
3 Takagi K Okabe S (1968). I h e effects of drugs on the production and recovery processes of the stress lUcer. Japunese loumal of Pharmacologi/, 9-11.
4 Vien Dugc lieu (2006). Phuong phap nghien cihi lac dyng dui?c ly ciia cay thu6c tCr dugc th^o, Nha xuSt ban khoa li?c va ky fhuSt tr. 63 - 64,140 -141,142-143,149,311 - 320
Y Hpc TP. Hb Chi Minh * T^p 20*S66* 2016 Nghien cuu Y hpc
5 WHO (1999). WHO Monographs on Selected Medicinal Ngay nhan bai bao. 30/07/2016 Plants,295. j - . j , j ^ ^ ^ ^ ^ ^ ^ j ^ , 31/08/2016 6 Winter C ^ Kisley EA, Nuss GW (1962). Carrageenan induced ^^^^ P " ^ '"^" " ^ " ^' '^^
edema in hind paw of the rai as assay for anti inflaminatoiy Ngay bai bao duac dang: 25/11/2016 drugs. Proceedings of the Soaety Jbr Experimenlal Biology ami
Medicnie, in,544r5i7.