N g h i e n
CLFU- K y t h u a t
r
Sang loc tac dung ha glucose huyet cua cac
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phan doan djch chiet cau ky tir va buo'c dau
r
danh gia tac dung ha glucose huyet cua phan
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doan dich chiet co tac dung ro nhat
• • • o Do Thj Nguyet Que ', Nguyen Tran Thj Giang Hu-ong^
Vu Thj Tram', Dd Thj Ha Phuong'
'Dai hoc Dirac Hd Ndi, 'Dai hoc YHd Ndi,Dat van de
Ciing vdi su phat then cua ndn kinh td, ddi sdng ctia ngudi dan ngay cang eai thien, kem theo dd la su gia tang khdng ngirng cua cae benh mang tinh xa hpi va cpng ddng nhu ung thu, tim mach... trong dd dai thao dudng la mpt trong nhii'ng benh hiem ngheo vdi ty le gay tti' vong chidm vj tri thir 3, chi sau tim mach va ung thu '^'^'.
Thudc didu trj dai thao dudng thudng phai diing trong thdi gian dai, ben canh eac tae dung chinh mong mudn dat duge, thude e i n dam bao gay it tac dung khdng mong mudn va gia thanh didu tri phai d mirc ma da sd benh nhan cd the chap nhan. Do dd, viee nghien ciru sang loc, tim ra cac hoat chit ed ngudn gdc tu nhien, ehu ydu tir thuc vat, de diing iam thude didu tri dai thao dudng da va dang la xu hudng nghien etru etia eac nha khoa hpc tren thd gidi.
Theo kinh nghiem dan gian, nhidu vi thudc dugc sir dung de didu tri dai thao dudng trong dd ed cau ky ttr (thudng dugc dung kdt hgp vdi cac vj thudc khac). Mpt sd tae gia da bude d i u danh gia tac dung ha glucose huydt etia eau ky ttr... '^'^'. Dd tim hieu sau han vd tae dung ha glucose huydt ctia vj thude nay chimg tdi tidn hanh chiet xuit eae phan doan, sang lgc tae dung ha glucose huydt etia cae phan doan nay va budc d i u tim hieu tac dung ha glucose huydt CLia phan doan djch ehidt ed tae dung rd ret nhit tren mpt sd md hinh thuc nghiem.
Nguyen lieu va phu'O'ng phap Nguyen lieu
Qua cua cay cau ky mua tai Cdng ty Duge lieu trung uang 1 (Mediplantex), dugc kiem dinh
theo tieu chuin qui djnh tai DDVN III bdi PGS.TS. Vu van Didn - Trudng DH Duge Ha Npi, va duge t h i m djnh ten khoa hpe bdi PGS.TS T r i n Van On - Trudng DH Duge Ha Npi, la qua ctia loai Lycium sinense. Mill (Hp Ca Solanaeeae).
Chuan bi mau nghien etru
Duge lieu dugc iam nhd, chidt bing methanol, c i t thu hdi dung mdi d ap suit giam, hoa e i n thu duge vao nude sau dd dem l i e vdi cac dung mdi cd dp phan cue tang d i n : n- hexan, clorofoc (CHCI3), ethyl acetat (EtOAc) va butanol (BuOH) (hieu s u i t thu duge etia mdi phan doan tuang trng la: 3,28%, 1,66%, 1,90%
va 7,22%). c i t thu hdi dung mdi de thu dugc eae e i n tuang trng.
Doi tu'O'ng nghien eieu
Chupt nhit tring chung Sw/iss ea hai gidng, khde manh, trong lugng trung binh 18 - 22g, do Vien Ve sinh Dich td Trung uang eung eip,
Chupt cdng tring, ea hai gidng, khoe manh, trong lugng trung binh 180-200g do hoc vien Quan y eung c i p
Chupt dugc nudi 3-5 ngay trude khi iam thi nghiem, eho an thire an c h u i n do Vien Ve sinh Djch td Trung uang eung e i p vi udng nudc tu do, tai phdng thi nghiem Bp mdn Duge ly - Trudng dai hpe Duge Ha Npi.
Phu'O'ng phap nghien ciru
Phwang phip danh gii tic dung ha glucose huyet tren chugt gay tang glucose huyet bing streptozocin (STZ)
Gay tang glucose huydt eho chupt bing each tiem mang bung STZ 1 lidu duy nhit 150mg/kg
28 TAP CHI DUQC HQC - 2/2011 (SO 418 NAM 5!)
Nghien CLFU - Ky thuat
pha trong dung djch dpm citrat (pH: 4,5-5). Djnh lugng glucose huyet sau 72h, \wa chpn nhCrng chupt cd glucose huyet 2IO mmol/l vi chia thanh cac 16.
Cho chupt udng thudc 5 ngay, so sanh gia trj glucose huydt tai thdi diem trudc va sau khi udng thude de danh gia tac dung ha glucose huyet ctia cae Id nghien ciru. Song song tidn hanh Id chtrng (udng dung mdi pha thude) de so sanh.
Djnh lugng glucose huydt b i n g may do glucose huyet Johnson & Johnson. Mau de dinh lugng dugc iiy tir dudi chupt (bd di giot mau d i u tien).
Ty le phin tram ha glucose huydt sau khi udng thudc, so vdi trude khi udng thudc, duge tinh theo edng thtrc:
A - B
X = X 100 A
Trong dd:
X: T"/ le phan tram ha glucosse huyet (%)
A: Nong do glucosse huyet ngay trudc khi dung thuoc
B; Ndng dp glucose huyet sau khi diing thudc Phuang phap danh gia tie dung ha glucose huyet tren ehugt gay dai thio duxyng dang type 2 bang streptozocin va vitamin PP
STZ ed tae dung pha huy td bao p dao tuy, trong khi dd nieotinamid ed kha nang bao ve td bao p chdng lai dpc tinh eua eac chit dpe nhu STZ va alloxan. Cho chupt udng vitamin PP (lieu 110mg/kg), sau 30 phut tiem mang bung STZ (vdi lidu 50mg/kg) lien tue trong 2 ngay. Bing phuang phap nay ed the gay tinh trang dai thao dudng g i n gidng nhu dai thao dudng type 2 d ngudi '^•'''.
Sau tiem STZ 3 ngay (ke ttr lieu sau eiing), chgn nhirng chupt ed glucose huydt > 10mmol/l va chia thanh eae Id, eho udng thude 5 ngay.
Dinh lugng glucose huyet trude va sau khi udng thude de danh gia tac dung etia thude.
Phuong phap danh gia tac dung ha glucose huyet tren ehugt eong trang binh thuKmg
Cho ehugt udng thudc 5 ngay, djnh lugng glucose huydt (chupt nhjn ddi khoang 15 gid trude khi cho udng thude ngay thtr 5), so sanh vdi gia trj glucose huydt etia ehugt udng dung mdi pha thudc de danh gia tae dung ha glucose huydt. Song song tidn hanh Id chtrng udng gliclazid, acarbose.
XCF ly so lieu
cac ket qua nghien etru dugc xw ly theo phugng phap thdng ke y-sinh hpc. SCr dung Test student de so sanh cac sd lieu nghien ciru.
K§t qua nghien
CIJPUAnh hirdng cua cac phan doan djch chiit tren glucose huyit cua chupt gay tang glucose huydt bang streptozocin (STZ).
Chon ngiu nhien 7 con lam 16 chtrng tring.
L6 1 (n=7): chirng tring, cho udng dung moi pha thudc.
s d chupt edn lai gay tang glucose huydt bing STZ vi chia thanh cac 16:
- L6 2 (n=8): Chirng STZ, cho uong dung moi pha thuoc
- Ld 3 (n=9): udng c i n phan doan djch chiet hexan vdi lidu 0.86g/kg
- Ld 4 (n=8): udng e i n phan doan djch chiet clorofoc vdi lieu 0.44g/kg
- L6 5 (n=8): udng c i n phan doan djch chiet ethylacetat vdi lieu 0.5g/kg
- L6 6 (n=8): udng c i n phan doan djch chiet butanol vdi lieu 1.9g/kg
- Ld 7 (n=9): udng gliclazid vdi lieu 20mg/kg cac lieu tren tuang duang vdi lieu 26g duge lieu/kg chupt
Ket qua djnh lugng glucose huydt trudc va sau khi udng thudc (hoac dung m6i pha thudc) 5 ngay (tai thdi diem 4h sau udng thude) nhu sau:
Bang 1: Tic dung tren glucosse huyit cua cic phin doan dich chiit
Ld
Chirng trang (n = 8) Chirng STZ
(n = 6) DC n-hexan
(n = 7) DC CHCI3
(n = 7) DC EtOAc
(n = 7) DC n-BuOH
(n = 7)
Nong do dwang huyet trung binh (mmol/l) Oh
7,20 ± 0,25
12,82 ± 0,97
11,57 ± 0,84
16,89 ± 1,25
13,09 ± 0,74
11,74 ± 0,76
4h (5 ngay) 6,59 ± 0,29
p >0,05 16,43 ± 2,27
p >0,05 14,17± 2,45
p >0,05 17,71 ± 2,04
p >0,05 6,71 ± 0,79
p<0.01 16,79 ± 2,75
p >0,05 p: so gia tri glucose huyet v&i thai diem Oh.
T.APCHI DUQC HQC-2/2011 (SO 418 NAM 51) 29
Nghien
CLFU- Ky thuat
Nhu vay, a lidu thtr, chi ed phan doan djch ehidt ethylacetat (DC EtOAc) ed tae dung ha glucose huydt cd y nghla thdng ke.
Chiing tdi tidp tuc nghien ciru tac dung ha glucose huydt ctia DC EtOAc tren eae md hinh thuc nghiem.
Ket qua dinh gii tic dung eua DC EtOAc tren chugt gay dai thao du&ng dang type 2 bang STZ vi vitamin PP.
Thi nghiem dugc tidn hanh tren chupt edng va dugc chia thanh 4 16:
Ld 1 (16 chir-ng tring): chupt khong gay DTD, udng nudc
Ld 2 (16 chir'ng STZ): chupt gay DTD va cho udng nude
Ld 3 (16 chirng duang): udng gliclazid vdi lieu 20mg/kg can nang,
L6 4 (16 thtr thudc): udng DC EtOAc vdi lidu 300mg/kg
Bang 2: Tie dung tren glucose huyit cua chugt gay DTD bSng STZ va vitamin PP
Nong do glucose tJIwc do huyet trung binh ha GH
(mmol/l) M+SE (%) STT Ten to
Oh 4h (5 ngay) 1
2
3
4
Lo chirng tring (n= 7)
Ld chirng STZ (n= 6)
Ld chung duong (n= 7)
Ld thir thuoc ( n - 7)
6,10±0.22
19.18±1.81
16.10±1,43
16,66=1.28
6,54±0,23 p>0,05 19,32±1,88
p>0,05 9,91±1,26
p<0,01 7,71±1,05
p<0,01
38,52
51,33 P3/4>0,05 P- so gia tri glucose huyit voi thai diem Oh.
P3/4: so sanh gitra 16 3 va 16 4.
Nhu vay, sau 5 ngay udng thudc, DC EtOAc vdi lidu 300mg/kg can nang co tac dung ha glucose rd ret tren chupt cdng gay dai thao dudng dang type 2 bing STZ va ^ itamin PP.
Mpt l i n nti'a khing dinh tac dung ha glucose huydt ctia phan doan dich chidt nay.
Tren ca sd cic kdt qua dat duge, chimg tdi tidp tuc tidn hanh nghien ciru sau han tae dung eua phan doan djch chidt nay.
Ket qua danh gii tie dung DC EtOAc tren ehugt eong tring binh thtrang
Chudt cdng binh thudng (kh6ng gay tang glucose huydt), chia thanh 4 16:
L6 1 (16 ehirng tring): ehu6t udng nudc
L6 2 (16 chtrng gliclazid): uong gliclazid vdi lidu 20mg/kg can nang
L6 3 (16 chtrng acarbose): udng acarbose vdi lidu 7mg/kg can nang
Lo 4 (16 thtr thudc): udng DC EtOAc vdi lieu 300mg/kg can nang
Cho chudt u6ng thudc lien tuc trong 5 ngay De chu6t nhin d6i khoang 15h trude khi cho chu6t udng thudc ngay thir 5. Ket qua dinh lugng glucose huydt sau khi udng thude 5 ngay (d thdi diem 4h sau udng thude) duge ghi lai trong bang sau:
Bang 3: Tic dung tren chudt thudng STT
1
2
3
4
Ten 16
Ld chirng t r i n g (n = 16) Lo gliclazid
(n = 7) Lo acarbose
(n = 8) Ld thudc thir
(n = 18)
Nong do glucose huyet trung binh (mmol/l) Pi/I± SE
3,82 ± 0 , 1 2 1,61 ± 0 , 1 4
P2/1 < 0,01 3,95 ± 0 , 2 1
P3/1 > 0,05 2.97 + 0.13
P4/1 < 0,01
Ket qua bang tren eho thay, d chupt thudng, DC EtOAc va gliclazid cd tac dung ha glucose huydt rd ret. Acarbose kh6ng the the hien tac dung nay.
Ban luan
Kdt qua nghien etru sang Ipe tae dung ha glucose huydt tren chudt n h i t gay tang glucose huydt bing STZ eho thiy, d lidu tuang duang lidu. 26g dugc lieu/kg chu6t nhit, c i n djch chidt phan doan ethylacetate (DC EtOAc) cd tac dung ha glucose huydt rd ret. Tac dung ha glucose huydt ctia phan doan nay mpt l i n nira dugc khing dinh tren chu6t cdng gay dai thao dudng type 2 bing STZ lidu t h i p , tiem nhidu l i n kdt hgp vdi vitamin PP.
Tren chupt cdng thudng, d 16 chupt diing gliclazid, la thudc da duge ehirng minh ed tac dung kich thich tuydn tuy bai tidt insulin, tac dung ha glucose huydt the hien r i t rd trong khi dd d 16 chupt diing acarbose glucose huyet khdng khae biet so vdi 16 chtrng tring (udng dung m6i pha thudc), Acarbose la thude cd tac dung ha glucose huydt do wc chd canh tranh enzym a-glucosidase lam giam h i p polysaeehand d rupt Tuy nhien. trong thi nghiem nay chiing tdi diing chupt da dugc de nhin ddi 15h trude khi
30 TAP CHi DUQC HQC - 2/2011 (SO 418 NAM 51)
Nghien CLFU - Ky thuat
eho udng thude l i n eudi vi vay acarbose khdng the the hien tac dung. Nhu vay trong thi nghiem nay da loai trir anh hudng etia qua trinh h i p thu tai dudng tieu hda ddi vdi glucose huydt. Nhu vay T4 ed tac dung ha glucose huydt ngoai dudng tieu hda (nhu tac dung kieh thich tuy tang bai tidt insulin va/hoac giam qua trinh tdng hgp glucose tai gan, tang tinh nhay cam eua md dieh ddi vdi insulin), Tuy nhien, b i n g thi nghiem nay khdng the khing dinh thudc cd hay khdng cd tac dung wc chd h i p thu eac monosaecharid va polysaccharid d dudng tieu hda hay tae dung tang sir dung glucose d td bao.
Ket luan
Qua nghien ciru thuc nghiem chimg tdi rut ra mdt sd kdt luan sau:
Tren ehu6t nhit gay tang glucose huydt bing STZ, d lieu thtr, ehl ed c i n djch chidt phan doan ethylacetat eua eau ky ttr ed tac dung ha glucose huydt.
c i n djch ehidt phan doan ethylacetat etia eau ky ttr ed tae dung ha glucose huydt tren chudt edng gay DTD dang type 2 b i n g STZ tiem nhidu l i n kdt hgp vdi vitamin PP, tren chudt edng thudng.
Summary
The ethylacetate extracts of Lycium sinense Mill solanaeeae) showed hypoglycemic effects
in diabetic mice with induced hyperglycemia by streptozocin and in rats with diabetes induced by streptozotocin plus vitamin PP and also in normoglycemic ones.
Tai lieu tham khao
1. D.A. Rees and J.C. Alcolado, animal model of diabetes mellitus. In; Diabetes U K. Diabetic t/ledlclne,{2005) 22, pp: 361-362.
2. Dao Van Phan, Nguyen Khanh Hoa, Pham HUu Diin, Tac dung ha dudng huyet ciia bach truat, cau ky tir va cam thao nam tren chudt nhit tring. Tap chi nghien ciru Yhoc.{2005) tr. 38(5).
3. Islam S., Choi H., Nongenetic Model of Type 2 Diabetes: A Comparative Study, Intemational journal of expehmental and Clinical Pharmacology Vol. 79, No. 4, 2007, p243-249
4. Lenzen S. (2008), The mechanisms of alloxan and streptozotocin - induced diabetes, Diabetologia 2008:51(2), p216-26.
5. Nguyen Khanh Hoa, Dao Van Phan, Pham Huu Dien va cong su, Budc dau nghien cuu tac dung ha glucose mau ciia cau ky tir tren chuot rdi loan dung nap glucose va chudt gay dai thao dudng bing streptozocin, Tap chi nghien ciru Y hoc, (2007), tr. 77(5).
6. Ta Van Binh, Benh dai thao dudng tang glucose mau. A/XB y hpc,(2006) tr.13-15, 24-28.
7. World Health Organization, Definition and diagnosis of Diabetes mellitus and intermediate hyperglycaemia. In: Report of a WHO/IDF consultation, (2006), p 1, 2, 3, 10, 27, 37.
Nghien cuu bao che vien nen ibuprofen giai phong keo dai
Dat van de
Ibuprofen la mpt thude khang viem, giam dau, ha sdt, h i p thu tdt qua dudng tieu hda va ed thdi gian ban thai ngin (ti/2 = 2 gid), do dd ndu bao chd dang thude quy ude thi phai udng nhidu l i n trong ngay va ed the gay ra nhidu tae dung khdng mong mudn '''•°'.
Dang bao chd giai phdng keo dai (GPKD) eua ibuprofen dang dwgc cic nha khoa hpe tren thd gidi va trong nudc quan tam nghien eii'u n.6.7] do
Nguyen Thi Thanh Duyen - Le Thj Kim Anh
Tnrdng Dgi hgc Dugc Hd Ngieai thien duge nhii'ng nhugc diem etia dang bao chd quy udc. Trong edng trinh nay, ehiing t6i tidn hanh nghien etru bao chd vien nen ibuprofen 200 mg GPKD.
Nguyen lieu va phu'O'ng phap
Nguyen lieu
Ibuprofen (An Dp), hydroxy propyl methylcellulose E6 (HPMC E6), sap ong vang, avicel PH 101, dicalci phosphat, polyvinyl pyrrolidon K30 (PVP) (Trung Qudc), lactose
