TCYHTH&B s6 5 - 2014 67
DANH GIA TAC DUNG DIEU TRj CUA KEM BERBERIN 0,1%
TAI C H 6 VET THl/ONG MAN TINH
Nguyln Tiin Dung, Nguygn Ngoc Tudn, Nguyin Thj VSn Anh Vidn Bdng Qudc gia T6MTAT
Muc tieu: Ddnh gid tdc dung cOa kem Berberin 0,1% lin diin biin tai chd vd kit qud diiu tri vit thuang man tfnh.
Phtmng phap: Nghidn cdu tiin cdu, can thidp cd ddi chCrng dwQC thi/c hidn trdn 60 bdnh nhdn cd vit thirang man tinh didu tri tai Khoa liin vit thuang - Vidn Bdng Qudc gia, tir thdng 5 ndm 2013 din thing 2 ndm 2014. Bdnh nhdn duac chia Idm 2 nhdm mdt cdch ngiu nhidn: Nhdm A: 30 bdnh nhdn dip vit thirang bing Silvirin 1% do An Dd sin xuit vd nhdm B: 30 bdnh nhdn dip vit thirang bdng kem Berberin 0.1% do Khoa Dirpv: - VBQG cung cip. Hai nhdm b$nh nhdn 6u^ theo ddi vd so sdnh cdc ch! tidu diin biin t^i cho vit thuang trdn Idm sdng, dSc diim chung vi khuin bi m^t vd diin biin md bdnh hQc t$i chd vdt thuang.
Kit qua: Tiin triin t$i chd vit thuang nhdm B tdt rd rdt han nhdm A trdn cdc chl tidu theo ddi:
Gidm tiit dich, giam vidm bd mdp vit thuxrng. xuit hidn td chirc hat do dep mdm mat vd biiu md thu h^p vit thirang. Sd ngdy diiu tri trung binh d nhdm B ngin hon so vdi nhdm A (29.2 ±12,5 ngdy so vdi 38.3 ± 11,7 ngdy). Vi khuin gdp d bi m0t vdt thu<mg phong phO vd chOng loai. gdp nhiiu Id P.aeruginosa vd S.aureus. K. pneumonia. Md bdnh hgc tai chd vit thirang cda cd hai nhdm tiin triin tdt idn theo thdi gian, d nhdm B biiu hidn rd rdt han so vdi nhdm A.
Kit luan: Kem Berberin 0,1% cd tdc dung tdt trdn kit qud diiu tri t?i cho vit thuung man tinh.
TiF khoa: Vit thuang man tinh, kem Berberin. nhiim khuin vit thirang. gidi phiu b$nh If'.
Aim: Evaluating the local effect of cream Berberin 0.1% on chronic wound
Method: A prospective controlled cohort study was performed on 60 chronic wound patients who were treated by either cream Silvirin 1% (group A) or cream Berberin 0.1% (group SJ. All patients hospitalized to Department of Wound Healing, NIB from May 2013 to February 2014.
Result: Local wound manifestation of group B were better than group A in term of wound exudate, peri-wound and local inflammation. Average length of hospital stay in group B were shorter than in group A (29 2 ± 12,5 vs 38 3 ± 11.7 days respectively). In both groups, common isolated wound bacteria were P.aeruginosa. S.aureus and K. pneumonia . Changes of local wound histopathology in group B was better than in group A: reduced inflammatory cells, increased the amount of fibroblast.
Conclusion: Cream Berberin 0.1% has positive effects on chronic wounds Keywords: Chronic wound. Cream Berberin. Local infection, Histopathology.
Phin bi0n khoa /ipc TS Nguyin Hai An
68
LDATVANOe
Vet thu-ong man tinh (VTMT) Id vit thu'ong (VT) (co the du'oc didu trj hodc khSng du-oc dieu tri) sau 3 thdng khdng khoi. Theo tdc gia Gottrup, 2004 c6 toi 1-2% ddn so 6 cdc nu'd'c phdt t r i l n c6 VTMT. S6 lu-gng b6nh nhdn ndy c6 the tdng ty 1$ thudn voi s y xuat hien ngdy cdng pho bien cdc b6nh gSn lien voi dieu kifen cuOc s6ng nhu-: Oai thdo du'dng, b6o phi, tim mgch [5,8],
VTMT chdm lien thu'O'ng Ii6n quan d^n rat nhi^u yeu to bat thu'i'ng, mgt trong so d6 theo tdc gia Warriner vd Burrell, 2008 cdc yeu t6 nhu' NK (NK) VT, s y tod"! mdu t6 chCrc, tinh trang thieu oxy, te bdo kh6ng th4 di cu- vd chan thu'ong Id nhiing nguyen nhan ddn td'l mpt VT chuyen thdnh MT, chdm lien, thgm chl khflng lien du'oc [17].
M(>t thyc trgng dgt ra d6i vd\ hau h6t cdc nhd Idm sdng Id lya chpn thuoc tgi ch5 cQng nhu' vdt li$u st> dgng de thay bdng hodc che phu VT giup khdc phyc nhO-ng y6u t6 bat thu'ong cua VTMT Id h^t su-c can thiet vd Id m^u ch6t giCip VTMT c6 the li^n d o o c . Trong dd vi§c sir dyng cdc thu6c c6 nguon goc tir thyc vdt Id mOt u'u ti&n trong y hpc hipn dgi vl n h i l u ddc tinh n6i trfli cua n6. Berberin Id alkaloid t h y c vdt thuOc nhflm isoqulnolin, tdch chiet tir cdy vdng ddng, hodng Ii6n gai (cosinium gagbep- myrtaceae), da du'pc bdo c h l 6 n h i l u dgng khdc nhau phyc vy cho nhieu chuyfen khoa Tgi Vi$n Bong Quoc gia, ndm 2008, Berberin da du'pc bao che 6 dang dung djch, bu-d-c dau du'oc bdo c h l o dgng kem de phyc vu d i l u trj V T c^p tinh, v l t bong vd cho nhOng k i t qua dieu trj tot trdn kha ndng khdng khuan, vd kich thich tgo tdn mgch, tgo to chipc hat, bieu m6 h6a VT [2, 3], Tuy nhidn Berberin dang kem mdc du d y p c bdo che nhyng chu-a c6 nghifen CLPU ndo ddnh gid tdc dyng cua n6 tr§n VTMT. X u l t phdt tir 66 chung toi trien khai nghidn ct/u de tdi:
"Bdnh gid tdc dyng dieu tn cua kem berberin 0 , 1 % tgi che VTMT".
2. D6I TUONG VA PHUUNG PHAP NGHIEN COU 2.1. Ddi t y o n g nghi§n cO'u
60 BN bl cac VTMT do cdc nguydn nhdn khdc nhau vdo d i l u tri npi tru tgi Khoa dieu trj LVT- Vidn Bong L§ HOu Trdc, ti> thdng 5 ndm 2013 d i n thdng 2 nam 2014.
BN du'oc chia ldm 2 nhom mOt cdch ngdu nhidn: BN c6 du tidu chulin vd d i n g y tham gia nghidn ciru du'pc chpn ngau nhien neu BN c6 so vdo vidn cuoi cung Id so chdn thi xep vdo nhom A vd BN cd so cu6i cung Id so je xgp vao nhom B.
Nh6m A: 30 BN d^p V T b^ng Silvirin 1%
do An Dp s^n xuat
Nhdm B: 30 BN dap V T bdng kem Berberin 0 , 1 % do Khoa D u - o c - V B Q G cung cap.
2.2. Tieu chuan lo^l tru>
- BN bj VTdo ung t h y hodc xg trj - BN bi cdc VTngflc ngdc phCi-c tgp - BN bj VTthdng vdi 6 khd'p 2.3. Vdt tu* nghien cu>u
- Kem Berberin 0 , 1 % do khoa Du-pc - VBQG san xuat
- Md' Silvirin 1 % do An 06 san xuat - Dung djch Natricolid 0,9%
- Kim sinh thiet biopsy punch 2.4. Phu-ong phap nghien cu'u
2.4.1. Nghidn ciru lam sdng
Tat ca BN vdo vidn deu du'pc ddnh gid vd theo doi cdc chl tidu toan thdn vd tai chd VT;
- Tuoi, gidi, bdnh man tinh kdm theo - D | c diem cua VTMT: Loai hlnh VT, cdn nguydn, thd'i gian ton tai VT; vj tri, di$n tich, d§
sdu cua VT; Tinh trang viem ne xung huylt, tinh trgng dich xuat tiet djch mu, tinh trgng bilu md hda.
Nghidn cO-u tdc dung cua kem Berberin 0,1%. BN tham gia nghidn cO'u d y p c chpn vd chia nhdm A, B mdt cdch ngau nhidn. Sau khi ddnh gid ddc diem tgi ch6 t6n thu'ong, dypc
TCYHTH&B so 5-2014 69
t i l n hdnh thay bdng VT 1 lan/ngdy vd ddp thuoc m& Silvirin 1 % vd'i nhdm A vd kem Berberin 0 , 1 % vd'i nhdm B. Theo ddi ddc diem dien b i l n tgi chd VT sau khi ddp kem Berberin 0 , 1 % hodc Silvirin 1 % .
2.4.2. Nghien cOu c$n lam sdng
* Xet nghidm vi sinh vat tai cho VT vd khang sinh d o d i f p t : lam tai labo vi sinh - VBQG: Bdnh pham sau lay de xdc djnh vi sinh v$t vd ldm khdng sinh do, Xdt nghidm vi sinh vdt tai chd VT du'oc t i l n hdnh tgi 3 thd'i d i l m 6- ca 2 nhdm A vd B:
- TO: Khi BN mdi nhdp vidn
- T10: Sau 10 ngdy su' dyng kem Berberin 0 , 1 % , Silvirin 1 %
- T20: Sau 20 ngdy sir dung kem Berberin 0 , 1 % , Silvirin 1 %
Xdt nghidm xdc dinh lodi VK: Su- dung ky thudt cua Ivanov N.A vd Danilova E.G (1984).
Gi>i b$nh pham ve khoa Cdn Idm sdng - VB, xdc djnh VK mdu bSng mdy djnh danh VK VITEX 32.
+ Xit nghidm mo b$nh hgc VT: Cdc VT d y p c t i i n hdnh Idm tidu bdn sinh t h i l t md: Tien
hdnh sinh thiet md VT bdng dyng cu sinh t h i l t (biopsy punch) vdo 3 thd'i diem: Khi vdo vidn (TO), ngdy thi> 10 (TIG), ngdy thO' 20 (T20) sau ddp thuoc Silvirin 1 % , hodc kem Berberin 0 , 1 % . Bdnh p h i m sau l l y d y p c c6 djnh bdng dung djch Fprmol. G i i i b^nh pham xuong Bp mdn Giai phdu bdnh. Hgc Vidn Quan Y Idm tidu ban giai phau bdnh ly,
2.S. XCP ly s 6 lidu
So lidu thu du-p-c trdn cdc chi tidu Idm sdng vd cdn Idm sdng cua 2 nhdm A vd B du'oc so sdnh de rut ra ddnh gid tdc dyng cua kem Berbenn 0 , 1 % . So lidu du-oc su- ly' bdng phan m i m R. Version 2.12.2.
3 . K £ r Q u A
3.1. €)|ic d i l m BN n g h i e n c(pu
BN nghidn cu-u c6 tf 10 nam/nO- Id 53/7 (7,57), dd tuoi trung binh Id 43,33 ± 14,97 t u l i , didn tich VT nghien ci>u t y o n g doi rOng 37,56
± 11,2 c m ^ VT ton t^i trung binh 4,12 ± 0,35 thdng. Nguydn nhdn gay ndn VT gdp nhieu do ty dd vd c h i n thu-ong c h i l m 58% (Bieu d l 1).
• Lo^ttydS
• Dii du'ft-ns
• T4C mach
•Tai ngn I • Khac Bieu do 1. Phan bo BNtheo tac nhan gay VT Bdng 1. PhSn b6 BN theo d^c diem VT va b#nh ly k i t hqp E)$c di^m
Vl tri VT Chi difdi CCing ci,it
Khic S6VT 1VT 2VT 23VT Benh ty kit hiyp
1 benh 2b^nh
£ 3 benh
Nhom A (n=30) N
12 20 10 12 15 3 22 6 2
%
40 66,7 33,3 40 50 10 73,3
20 6,7
Nhom B (n=30) N
15 22 11 10 15 5 24 5 1
%
50 73,3 36,7 33,3 50 16,7
80 16,7
3,3
Nhin xit: VT ciing cut gap vai ty l# nhiiu ntiat a ca hai nh6m BN. BN ab 2 VT vS cd 1 tj^nh 1^ nOi ho$c ngoai khoa l<et hop chiim ty [$ cao 6 ca 2 nhdm BN.
Bang 2. Phan b6 BN theo d? sau VT (phan loei theo hoi LVT Hoa Kjr)
O^sau
1 II III IV
Nhom A (n=30) N 3 5 19 3
%
10 16,7 63,3 10
Nhom B (n=30) N 2 6 20 2
%
6,6 20 66.7
6,6 Nh$n xet: Ca hai nh6m A vS B gjp vet lo6t dO III chiim t} 1$ cao (Nh6m A 63,3% vi nhdm B:
6,7%)
Hinh 1. Le Van T (SBA:1336): Vet loet viing cung cyt du'pc d i p Silvirin 1 - T10 VT c6 TCH,
0
giam viem nhu'ng mep VT con viem n l t l y do, T20 VT glim viem n l , TCH do dep ho-n va CO bilu mo hoa tu m6p VT vdo.
Hinh 2. BN Ngd Viet H (SBA: 1243): Vet loet do ty de vung cCing cyt du'pc dap Berberin 0,1 - T10 VT c6 TCH hai nhcft, VT giam vigm n l , T20 VT c6 TCH do dep, bieu mo hod thu hep VT
3.2. Didn b i l n VT n g h i e n CLFU
Bang 3. Diln b i l n VT khi d i p Silvirin va Berberin (Hinh 2 vii 3)
^ \ 0|c diem Thd'i d i l r n ^ ^
Tiet dich t?! cho VT
TO(n=60) (1) Nhi^u
T10 Nhom A
(n"30) (2) Vira
Nhom B(n=30) (3|
Vila
T20 Nh6mA(n=12)
(4) Vila
Nh6m B (n°19|
(5) It
TCYHTH&B so 5 - 2014 71
Viem tgi cho
To chi>c hgt
Bieu mo hoei
Phan O-ng dj Crng Nhiet d$ CD the Di?n tich VT "
(cm') pCl
Viem bir mep:
Bi/ m^p n l Xung huyet
Nhgl. xlu, th^nh d^rng flirng
Chua CO
37,33 ±0,28 A38,36± 14,29 B36.15± 19,41
ViSm bcf mep c6 giam:
B6 mep ne nhe. xung huylt nhe Nhol, n l , thanh
di,rng
Xult hien bilu m6 ti> bd m6p
VT Khong 37,51 ±0,31 37,65 ±12,83
Viem bo mep c6 giam.
Bo- mep n l nhe, Xung huyet nhe
Do dnh vdng (miiu berberin)
thdnh dyng Xuat hien bieu m5 tCr bi> mep
VT Khong 37,51 ± 0.31 34,27 ±15,44
Viem nhe, Bd mep khong nl, khdng xung
huyet Nhol, ne, mim
mgi
Bieu mo hoa thu hep dien tich VT (kh&ng dang kl)
Khfing 37,40 ± 0.22 32.62 ±13,18
Viem nhe, Bd m6p khflng n l , khflng xung
huyet Do anh vang,
mem mgi
Bieu mfl hoa thu hep VT, ho$c TCH che kin VT
Khong 37.40 ± 0.22 23,19± 11,41
Nh6m A: Pi.2 > 0,05. Pi-* > 0,05. P2.4 > 0,05 Nh6m B: PLS > 0,05, Pi.s < 0,05, Pis > 0,05
Nhdn xit: Berberin khdng gdy phan Ci'ng dj Lfng. Ci hai nhdm VT tiln triln tit hon theo thd-i gian: Giam tilt dich, giam vidm bd mdp VT, xuat hidn to chu-c h^t dd dep mim mgi vd bilu md thu hgp VT (nhu-ng tot hon rd d nhdm
ddp Berberin). Didn tich VT thu hep rd rdt o ngdy thCp 20 d nhdm B cd y nghTa so vdi tru-d-c dilu tri (P<0,05). Khdng thiy sy khdc bi$t rd r0t ve kich thu-dc VT d nhdm A vd nhdm B o thdi diem ngdy 10 sau dilu trj.
Bdng 4. Ty I9 phlu thugt thdnh cong
Lofi phlu thu$t
Gh^p da manh Chuyen vat da Cong
Li^n l^n dau Nhom A {n=30)
N (%) 4(13,3) 12 (40) 16 (53,3)
Nhom B (n=30) N {%) 3(10) 18(60) 21 (70)
Phai phluthu$tl9i Nhom A (n=14)
N(%) 8 (64,3) 5 (35,7) 14(100)
Nh6m B (n-9) N(%) 7(77,8) 2 (22.2) 9(100) Nhin xit: 100% BN phii phSu thuSt NhOm B c(5 ty 10 BN phSu thuat lien ngay lin diu cao hon nh6m A (70% so vd'i 53,3%). Trong so BN phai phiu thu$t lai chij y i u 1^ ghep da bo sung (nhdm A: 64,3% va nhdm B: 77,8%).
Hlnh 3. BN Le Vdn T (SBA:1336): Lo6t do ty d l cijng cut du'oc dap Silvinn 1%, liln ngay l l n d i u phlu thugt chuyin vgt
72
Hinh 4. Lfi Trong C (SBA: 1945): BN lo6t do ty d6 dup-c dip Bertjerin 0.1% liln ngay lln diu phlu thu|t chuyin vgt.
Hinh 5. BN Pham Quang V (SBA: 5280): VT dap Silvirin phai khau lai vat Bang 5. Tho-i gian dilu trj trung binh
Nhom A (n=30) B (n=30) P
X t S D 38,3 ±11,7 29.2 ±12,5
Min - Max 16-62 14-52
<0,05
Nh$n xit: Nhdm B cd so ngdy dieu trj trung binh ng^n hon so vd-i nhdm A, SM" khdc cd y ngMa thing kd vdi p <0,05.
3.3. K i t qud c l y khuin
Bang 6. Phdn bd BN hai nh6m A vS B theo chiing VK xult hi#n tren b l m$t VT
VK
So mSu (*) S. avreus P. aenjglnosa K. pneumonia Aci.Baumanii Ent faeclum Ent.cloacae S hominus S. scfon Pro. Mirabllis
P aenjglnosa - K.pneumonia S. aureus - P.aeniginosa S.aureus - Ent.faecium
TO Nh6mA
(n=30) N(%) 22 (73,3)
5(16,7) 6(20) 2(6.7) 1 (3,3) 1 (3,3) 1 (3,3) 2 1 (3,3) 1 (3,3) 1 (3,3)
Nhom B (n=30) NC/.) 23 (76,7)
4(13.3) 6(20) 3(10) 2 6,7) 1 (3,3) 1 (3,3) 1 (3,3) 1 (3,3) 1 (3,3) 1 (3,3) 1 (3.3) 1 (3,3)
T10 NhlSmA
(n=25) N(%) 15(60)
2(8) 2(8) 1(4) 1(4) 2(8) 3(12) 1(4)
1(4) 1(4) 1(4)
Nhom B (n=18) N(%) 8(44) 1 (5,5) 2(11,1) 1 (5,5)
1 (5,5) 1 (5,5) 1 (5,5)
1 (5,5)
T20 Nh6mA
(n=10) N(%) 6(60) 1(10) 1(10) 1(10) 1(10) 1(10) 1(10)
NhomB (n=11)
N(%) 3(27,3)
1(91)
1 (9,1) 1 (9,1)
TCYHTH&B so 5-2014 73
Nh$n xit: VKgdp 6- be mdt VT phong phO v l chung lo$i, gdp n h i l u Id P.aeruginosa vd S.aureus. K. pneumonia. X u l t hi$n cdc VK c o hdi S. scion, Pro. Mirabllis... S y x u l t hidn cdc chOng VK ndy giim theo thdi gian o ca hai nhdm A vd B. 6" thdi d i l m T20 ty 1$ s l m§u (+) 3v4. S ^ b i l n d d i mo b^nh h9c tai chd VTMT
d nhdm A cao hon so vd-i nhdm B. Nhdm B khdng ttily su- xuat hidn cua P.aeruginosa, S.aureus vd Aci.Baumanii. nhu-ng o nhdm A vdn cdn 2 mdu (+) vdi P.aeruginosa, vd S.aureus.
Bdng 7. S y b i l n doi m6 t)|nh hpc tgi chd VTMT
Th^j dilm VOng A (n=8) Vung B (n=g)
Tin thuong todn bfl I6p da, mo lifln kit du'vi da bi phii viem, cdc khe gian bdo gidn rpng, rai rdc thiy hing clu trdn nln dich ri vlflm, nhilu t l bdo viSm md chO y l u Id bgch clu Lympho,cd khi tgo thdnh tiing ddm bgch cau (Hinh 6-1) Tlbdoviflm:17.5±2,3/OVS NBS: 5.7 ± 0,6/OVS
Tin thuong todn bfl Ifl^p da, mfl lifln kit dift^i da bj phCi vjflm, cdc khe gian bdo gian rflng,rdi rac cfl hing c l u tren nln djch ri vifim, nhilu t l bdo vlflm, chu yeu Id bgch cau lympho (Hlnh 8-2).
T l bdo viSm: 16,3 ±2.7/DVS NBS:5,3±0,5/OVS Cl viing trung tdm VT gip hinh anh nln VT Id
md lien kit gIm cdc si?! tgo keo nim sdt nhau, cdc te bdo sp'i va nguyen bao so'i IL co s{f thdm nhilm rSI rdc cdc t l bao lympho, Co hlnh anh tdng sinh cdc t l bdo gai tir mdp VT vdo (Hinh 8-3).
Te bao viem. 12,8±2,4/DVS NBS 7,2±1,9/DVS
Trung tdm VT chiing 161 bit g|p hinh anh nln VT Id md liSn kit ddy gIm cdc scri tgo keo ndm sdt nhau. cac te bdo so'i vd nhilu nguyen bdo so'i. cd sy thdm nhiem rai rdc cac t l bdo lympho. Cd hinh anh tang sinh cdc t l bdo gai tir mlp VT vdo (Hinh 8-4).
T l bao viem: 8,2 ±1.6/DVS NBS-TBS:11,6±1,7/OVS 0 vung ria VT gdp hlnh anh bilu md hoa tir bd
mdp VT vdo: dd Id hinh anh cdc t l bdo gai tSng sinh, dang bd vdo ddy VT, phia dudi Id md llSn kit xc vdi khd nhilu t l bdo &q/'\, xen lln cSc bgch c l u da nhdn, t l bdo lympho va dgi thg-c bdo (Hinh 8- 5).
Tlbdovi6m:7,2±1.7/DVS NBS. 10,01 ±1,6/DVS
ViJng ria VT ggp hinh anh bilu md hoa tir bit m6p VT vao: dd la hlnh anh cdc t l bdo gai tdng sinh, dang bd vdo ddy VT. phia dud-i la md 1i§n ket xo vdi kha nhieu t l bao si?\, xen lln cdc bgch clu da nhdn, te bdo lympho vd dgi thyc bdo (Hinh 8 - 6) T l bdo vigm; 4,9 ±1,5/DVS
NBS: 13,1 ±1,2/0VS
Nh$n xit: Hlnh anh md bdnh hgc cOa cd hai nhdm A vd B gdp nhOng hinh anh dien hinh cua VTMT, Md b$nh hpc cua ca hai nhdm b i l u hi0n VT t i l n t r i l n tot Idn theo thd-i gian S6
lu-p-ng te bdo vidm giam d i n vd s6 lu-o'ng NBS tdng d i n theo thd-i gian 6 ca hai nhdm A vd B (nhu-ng thay rd r$t hon o nhdm B).
74
Hinh 6.0?c diem mo b^nh hoc cua 2 nh6m A va B * c4c then dilm nghiSn cini xem tren vSt Idnh x 400 vax 1000
Thirl dilm
4. BAN LUAN
4.1, BN nghien ci^u vi diin bign lam sdng VT khi alp Berberin 0,1%
Trong nghifin ci>u nay 60 BN c6 VTMT du-a vdo nghien ci>u difp'c lifa chpn mOt cdch nglu nhiSn l<hi tier hdnh chia nh6m de Sip thu6c Silvirin 1% vd Berberin 0,1 - Trong th&i gian nghiSn ciju BN c6 VTMT du'pc l^a chon theo ti^u chuan cua hOi lien VT MJ [12] (Id nhu'ng Bn c6 VT dupe dieu trj hay khang dieu trj- nhu'ng 3 thang kh6ng lien). BN difpc chia nh6m ngSu nhiin: BN c(5 so vdo vi0n chSn diFa vdo nh6m ddp Silvirin 1% va so vdo vien le du'a vdo nh6m ddp Berberin 0,1%. Viec chia nh6m ngdu nhien ndy dam bao diipc tinh
khdch quan khi tien hdnh phdn tich so sdnh tdc dung cua hai thu6c. Tuy nhien mOt vin 6k djt ra vdi cdc nghiSn ciJu khi chpn BN cd VTMT Idm doi tu'png nghiSn cCfu 36 Id: Hau hit cdc BN c6 VTMT diu c6 tif mit den hai b§nh IJ nji hodc ngoai khoa di kem. Cdc b#nh ly kdm theo ndy anh hu'O'ng rat Idn t<M qud trinh lien VT.
Boi vdy trong nghidn ci>u ndy ngodi vi§c so sdnh ngang giu'a hai nhdm ddp thu6c khdc nhau chiing tdi cung d|t v4n de xem xdt vS ddnh gid dien bien ciJa VT tru'6'c vd sau nghifin ci>u (vol thiet ke nhu Id mi5t nghidn cilu dpc ci can thipp vd so sdnh tru'd'C sau dieu tri). K6t qua nghien ci>u cija chijng tdi chl ra rd rdng dieu ndy; Khi BN trong nhdm nghign ci>u c6 nguydn nhdn dan td-i VT khd phong phil nhi/
lodt ty dd (trdn BN tai biin m?ch mdu ndo, lidt
TCYHTH&B so 5-2014 75
tuy do c h i n thu-ong cOt s6ng), lodt do ddi du'dng, tdc mgch, su- di,ing corticoid ddi ngdy de d i l u tri cdc bdnh ly ndi khoa nhu- luput ban dd. hOi ChCrng curshing... Han nO-a 2 nhom BN nghidn cu-u khdng chl cd 1 VT md ton tgi tCi- hai VT trd Idn c h i l m t f le cao (Bang 1, 2), VT chu Igi yeu ton thu-o-ng dp III (63,3% nhdm A vd 66,7% nhdm B). K i t qua ndy cOng phu h^p vdi nhdn djnh trong nghidn cCru cua tdc gia Nguyin T i l n DQng vd c^ng SM- khi nghidn ct!ru v l tdc dicing cua trj lidu hot dp lu-c dm trong dieu tri VTMT [1].
G l ddnh gid tdc dgng cua Silvirin 1 % vd kem Berberin 0 , 1 % chOng tdi lu-a chpn thdi d i l m ddnh gid Id tru-dc khi d i p thuoc, 10 ngdy vd 20 ngay sau ddp thuoc. Do BN cd VTMT vdo d i l u trj vdi chCing tdi da phan dd du-p-c dieu trj tgi nhd hodc cdc CCT sd- y t l khdc khdng khdi, bd-i vdy t i l n t r i l n cua cdc VT ndy thu-d-ng chdm, mdt khdc vide kiem sodt vd d i l u tn cdc b0nh 1^ n0i vd ngogi khoa k i t hpp d i n on djnh Id c l n t h i l t de dam bao ^ l u kidn thudn ipi nhat cho qud trinh lien VT 6- VTMT. Ben cgnh dd qud frinh LVT cua mOt VT ndi chung vd VTMT ndi ridng chiu tac ddng cua rat nhieu cdc y l u t l khdc nhau: N h i l m k h u i n tai chd VT, mdi tru'dng tai chd VT khdng thugn Ig-i cho qud trinh tgo to chu-c hgt vd bieu md hod. Cdc nghidn ci>u v l LVT d- mCi-c te bdo vd phdn tu- k i t ludn r i n g cdc y l u to lien quan td-l qua trinh LVT cua VTMT cd lidn quan tdi thieu hgt mgch mdu tdi VT [13], ho$c chdn dp da ddn td-i sinh mgch khdng thda ddng [7,13], di cu- t l bdo bj tdn thu-o-ng, sg- kich hogt vd bigt hda te bdo SLcng khdng binh t h u d n g [5].
Silvirin 1 % do An B p san xuat la mOt t h u l c dgng kem, c6 tdc dgng khdng khuan. tgo mdi tru'dng am kich thich qud trinh LVT dd du-pc nghidn cu-u nhieu vd trd thdnh mdt trong cdc thuoc thu-d-ng xuydn du-pc k h u y i n cao SLF dyng trong qud trinh chdm sdc VT khdng chf vdi VT c l p tinh md cdn vd-i ca cdc VTMT [11]. Kem Berberin 0 , 1 % du-p-c khoa Du-gc - VBQG cung
cap dgt tidu c h u i n co- so-, dd du-pc cai t i l n de nang nong dp Bertaerin tO 0 , 1 % Idn 1 % nhd thay doi hoat c h i t Ngoai tdc dgng khdng khuan cdn cd tdc dgng kich thich qud trinh tgo tdn mgch vd tdng sinh nguydn bdo sp-l, kich thich qud trinh bieu md hod VT [2, 3]. Trong nghidn ci>u nay chOng tdi nhdn t h i y ci hai nhom BN d i p Silvirin 1 % vd ddp Berbenn 0 , 1 % , VT d i u cd bien c h u y i n tot Idn theo thdi gian. ChOng tdi khdng gdp tru-dng hpp BN ndo cd phan u-ng dj O-ng, k i t qua ndy cung phCi hpp vd-i nhdn djnh cua tdc gia Tuhin K.B vd cOng sy- khi nhdn xdt r i n g Berberin cd tdc dgng Idm mdt (khi so sdnh vdi tdc dgng hg nhigt cua sodium salicylate) [18] vd nghidn ci>u cua tdc gia Nguyen Ngpc Tuan khi nghidn ciru tdc dyng cua kem Berberin 0 , 1 % Idn didn bien VT bdng ndng [3]. Nhu-ng d i l n bien VT d nhdm ddp Berberin 0 , 1 % t i l n t n i n rd r0t hon, the hign tinh trgng vidm tai ch6 VT, s y xuat hidn vd tinh chat t l chu-c hgt, ddc bidt Id kh^ ndng b i l u md hod thu hep didn tich VT cug nhdm ddp Berberin 0 , 1 % d" ngdy thu- 20 sau d i p t h u l c cung nhu- so vd-i nhdm d i p Silvirin 1 % (Bang 4). K i t qud ndy cOng phu hpp vd-i nhdn djnh cua tac gia Phgm Tnnh Qudc Khanh khi nghien cO-u tdc dung cua Kem Berberin 0,05% trdn BN cd VT bdng ban tay vd k i t qua nghidn cu-u dd tdi cap CO s d VBQG khi so sdnh tdc dyng cua Kem Berberin 0 , 1 % v d i Silvirin 1 % trdn VT bdng ndng [2]. Ve tac dgng khdng mong m u l n , trong nghidn cii-u nay chCing tdi nhdn thay kem Berberin 0 , 1 % cd mdu vdng d^c tru-ng do dd khi d i p len VT thu-d-ng d l Igi mdu dnh vdng tren b l mgt bet thyo-ng n l u d i p t h u l c dai ngdy vigc ndy cd anh hu-d-ng ddi chut td-i nhgn djnh vd ddnh gid VT trdn lam sdng. Cdn d i p Silvirin 1 % nhu- n h i l u nghidn cu-u khdc cung ddnh gia, Silvirin thu-d-ng hod ddng sau 24h vd n l u d i p dai ngdy thu-dng tgo thdnh Idp gia mgc trdn b l mat VT (Hinh 7).
76
Hinh 7 VT sau b i c bo g j c nhau kem Berberin 0,1% va sau khi l^m s?ch b i n g dung dich Natriclorid 0,9% nhung v i n c6 m i u i n h vang (1). VT d u ^ c d i p gac nhau Silvirin 1%, Silvirin hoa d i n g vS d l l;l
ioTJ g i i m?c tren be m^t VT (2).
Ve * e ( Qua phau thu$t: 100% BN nghidn cCru phai can thidp phdu thudt do nhdm BN c6 VT dd I, II (khdng phdi can thidp phdu thudt) lai thu-d-ng cd nhi4u han 1 VT vd nhfrng VT khdc Id nhOng VT dd ill hodc IV {bk budc phai can thidp p h l u thudt). Hon nO-a do lidn quan d^n thdi gian dieu trj, kha ndng ddp Crng v^ m$t kinh phi, kha ndng tdi phdt sau dieu tri vd cdng nhdm rut ngdn thd'i gian dieu trj cho BN ndn Chung tdi khdng chij tnfong dieu tri nOi khoa d^n khdi nhii'ng BN ndy. Trong nghidn ci>u cua Chung tdi nhdn t h i y ty Id BN lien ngay lan dau phdu thudt (Chuyin vat hodc ghdp da) 6' nhdm BN d i p kem Berberin 0 , 1 % cao hon so vdi nhdm d i p Silvirin 1 % (70% so vdi 53,3 - Bdng 6). S6 BN phdi phdu thudt lai a ca hai nhdm chu y l u Id phai ghdp da bd sung hodc khdu lai vat da do hoai ti> mdp vat, todc v l t mo do vidm chdn chl, hay chay mdu du'di vat da... Thdi gian d i l u trj trung binh, chung tdi n h j n t h i y a nhdm d i p Berberin 0 , 1 % du'oc rCit n g i n hon so vdi nhdm BN difpc d i p Silvirin 1 % Ket qua ndy cung phu hpp vdi nghidn ci>u cua tdc gid Nguydn Ngpc T u I n vd cdng sut khi nghidn cCru so sdnh tdc dung ciJa kem Berberin 0 , 0 1 % vd Silvirin 1 % trdn VT bdng ndng nhdn dinh: Thdi gian khdi cOa vet bdng ndng dd 11 vd dd ill du'pc dieu trj b i n g kem Berberin clorid d i u dupe rut n g i n hon sp vdi nhdm chiing 1-2 ngdy, p<0,05 [3]. Cung nhu tdc gia Ang ESW, Lee ST, Gan CSG (2001) nghidn cCru tdc dgng cua m d MEBO China berbenn tai chd vet bdng ndng cOng nhdn t h i y MEBO dd nit n g i n thdi gian dieu trj cdn 70% so vdi phifpng phdp S T truyen thong, giam 8% gid thdnh d i l u tri. Cdc
tac gia coi thu6c MEBO n h u mdt "cudc cdch mang trong DT bdng cija Trung Quoc" [4]
4.2. B i l n d o i VK va g i a i p h d u b e n h ly tai chd VT d i p Berberin 0 , 1 %
c u n g vdi nghidn ci>u tdc dung i>c c h l VK, ngdy cdng cd nhieu nghidn cd'u tdp trung vdo tdc dung chdng vidm cua Berberin. NhOng nghidn ci>u ndy thu d u p e nhii'ng k i t qud kha quan, m d ra n h i l u then vpng Cpng dgng trong d i l u tri, ke ca nhu-ng bdnh ly vdn cdn nhilu nan giai nhu ddi thdo d u d n g , tim mach, ung thu...
Cdc nghidn cCru ghi nhdn vai trd Crc c h l cdc mediator vidm ciJa Berberin. Nghidn cCJ-u in vitro vd in vivo trdn chudt t h i y Berberin Ci-c c h l tao cyclooxygenase-2 (COX-2), do vdy Idm giam PGE2, c h i t ddng vai trd quan trpng trong qud trinh vidm [6]. Berberin Crc che tiet arachidonic acid til' thdnh phospholipid ciJa mdng t l bdo, s i dgng hidu qua cdo c h i t chuyen hod cua acid ndy. Berberin Crc c h l arachidonic acid ( M ) - gom ca thromboxane A2 t i l t ra tir t i l u clu... vd ngupc lai tdng t j o 6- keto-prostaglandin F1 alpha a tieu c l u . Do vdy, nd cd tdc dung lie chl giai doan khd-i phdt ciJa qud trinh vidm. Trdn Idm sdng, Berberin cd tdc dung Idm sach djch x u l t tiet, giam tinh tham thdnh mach, giam phii ne [10,16], Lindsei K 2010 nhdn t h i y Berberin Ci'C che NADPH oxidase do dai thuc bdo t i l t ra, do vdy cd tdc dgng antioxydant [14J. Hyun Woo jeong (2009) ghi nh|in Berberin thdng qua ho?t hda AMPK cOa dai thirc bdo - te bdo chu y l u ddp u-ng trong qud trinh vidm, u-c che hdng loat cdc mediator t i l n vidm, do dd giam ddng k l cdc c h i t LPS, goc acid bdo, goc oxy t u do... [9). Ang
TCYHTH&B so 5-2014 77
ESW (2001) nghien ci>u tdc dyng cua m d MEBO chCea Berberin so vd-i phu'ang phdp BT truyin thong tai chd v l t bong ndng nhgn thay MEBO cd tdc dgng kich thich l i l n VT, chong vidm [4].
Doi vd-i VTMT theo tdc gia Mustoe T 100%
cd VK tgi chd VT [12]. Trong nghidn cCru ndy k i t qua c l y khuin cua chOng tdi nhgn mdt ty Id cao so m i u du-o-ng tinh vdi VK (nhdm A 73,3% vd nhdm B 76,7%), VK be mdt VTMT rat da dang, ngodi nhu-ng VK hay gdp nhu- S.aureus.
Paeniginosa. K.pneumonia, Aci.baumanii.
chQng tdi cdn t h i y x u l t hidn cdc VK c a hdi nhu- Entfaecium, Entcioacae vd Pro. Mirabllis K i t qua d i l u tri tgi cho cug Berberin 0 , 1 % vd Silvirin 1 % cOng cd tdc dyng tot khi d' ngdy thi> 10 s6 m i u du'ong tinh vd'i VK giam rd rdt so vdi ^U'dc digu trj d" ca hai nhdm d i l u tri, d i l u ndy the rd ho-n d nhdm ddp kem Berberin 0 , 1 % khi d i n ngdy 20 chl cd 3/11 c h i l m 27,3% s6 mdu du'p'c c l y cd VK, han nO-a chCing tdi khdng t h i y s y x u l t hidn cua cdc VK S.aureus. Paeniginosa.
Aci.baumanii nhu- d thdi d i l m ngdy thii- 10.
Nhu'ng doi vd-i nhdm d i p Silvirin 1 % , d i n ngdy thu- 20 chOng tdi gdp 6/10 mdu du-p-c c l y cd VK vd vdn t h i y sg- x u l t hi$n cua cdc VK S.aureus, Paeruginosa, K.pneumonia, Aci.baumanii. K i t qua nghidn ci>u cua chiSng tdi cOng phan ndo phCi hp-p vdi nhdn dinh cua tdc gia Nguydn Ngpc Tuan vd cpng s y khi t i l n hanh nghien cu-u in vitro so sdnh tdc dgng i>c che VK giO-a kem Berberin clorid vd Silvirin 1 % nh$n thay:
Berberin clorid cd tdc dyng i>c c h l doi vdi 3 Chung VK q u i c t l Id E coil ATCC, S. aureus ATCC vd P. aenjglnosa ATCC. Kem Berberin clorid cd du-d-ng kinh vdng vd k h u i n Urang du-ang vdi kem silvirin (p>0,05), Trdn vet bdng thyc nghi#m, thuoc Berberin clorid cd tdc dyng Idm giam tong lu-p-ng VK trdn be mdt vet bdng sau 1- 2 t u I n dieu trj, p<0,01. S6 VT khdng moc VK d vDng NC (BT bdng kem Berberin) cao han h I n so vdi hai Id cdn Igi (du-p'c B T bdng kem Silvirin, nu'd'c muoi sinh ly 0,9%), p<0,01 [3].
B l mdt VTMT cd the l i l n du'p'c ngoai vi^c phai kiem sodt tot cdc bdnh ly ndi, ngogi khoa dy(?c hieu nhu- Id cdc nguyen nhdn tryc t i l p ho|ic gidn t i l p gdy ndn VTMT, thi vide phai
dam bao mdt dieu kign tot nhat cho qud trinh LVT tai chd VT d i l n ra thuan Ipi. Nhu' mdi tru'dng am, khdng cd VK, dinh du-5-ng tot, cdc yeu td kich thich qud trinh LVT nhu- cdc yeu to tang tnpang mach, tdng tru-d-ng bieu bl... phai du'pc dam bao ca ve so vd chat lu'png [12]
Nhd nhu-ng ddc tinh cua Sivirin 1 % vd Kem Berberin 0 , 1 % nhu- da trinh bdy d p h i n trdn.
K i t qua dl^n b i l n giai p h i u benh ly tai ch6 VT cQng b i l u hidn rd tinh y u viet hon cua kem Berberin 0 , 1 % so vdi Stivinn 1 % . The hign a sg- xuat hidn to cht>c md lidn k i t , cdc te bdo sp-i, vd tdng sinh cdc t l bdo gai thuc d l y qud trinh b i l u md hod tir bd- mdp VT thu hep kich thyd-c VT. Bdc biet so l y p n g cdc te bao vidm giam vd s6 lu-png NBS tdng Idn rO r0t theo thdi gian (Bang 8 vd Hinh 6)
K&T LUAN
Qua nghidn cO'u 60 bdnh nhdn cd v l t thuang man tinh, d y p c chia Idm hai nhdm, 30 BN ddp VT bdng VT bdng Berberin 0 , 1 % vd 30 BN ddp Silvirin 1 % . Cdc BN dieu trj npi tru tgi khoa L i l n Vet Thu-anng - Vidn Bdng Q u i c gia trong thdi gian tu- thdng 7/2013 d i n thdng 4/2014 chOng tdi rOt ra nhij-ng k i t ludn sau:
1 Berberin 0 , 1 % khdng gdy phdn O-ng dj u-ng. T i l n trien tai ch6 VTMT 6- nhdm ddp Berbeirin ^% tot rd rdt han nhdm d i p Silvirin 1 % trdn cdc chf tieu theo ddi: Giam t i l t djch, giam vidm b d mdp VT, x u l t hign t l chu-c hgt do dep m i m mgi vd bieu md thu hgp VT. 0 ngdy thO 20, dign tich VT so vdi tru-dc khi ddp t h u l c nhdm d i p Berberin 0 , 1 % thu hgp rd r^t han (23,19 ± 11,41 cm^ so vdi 36,15 ± 19,41 cm^), vd so vdi nhdm d i p Silvirin 1 % (23,19 ± 11,41 cm^ so vdi 32,62 ± 13,18 cm^). So ngdy d i l u tn trung binh a nhdm ddp kem Berberin 0 , 1 % n g i n han so vdi nhdm d i p Silvirin 1 % (29,2 ± 12,5 ngdy so vdi 38,3 ± 11,7 ngdy)
2 VK g^p a be m^t VT phong phu v l chung loai, gdp nhieu Id P.aeruginosa vd S.aureus. K. pneumonia, trong dd cd s y x u l t hi$n cdc VK c a hpi S. scion. Pro. f^irabilis...
S y xuat hidn cdc chung VK ndy giam theo thd-i gian d-ca hai nhdm d i p kem Berberin 0 , 1 % vd vd Silvirin 1 % . C" thdi d i l m ngdy 20 sau dieu trj
ty le sd m i u (+) d nhdm d i p Silviril 1 % cao hon so vdi nhdm ddp Berberin 0 , 1 % (60% so vd-i 27,3%). Nhdm d i p Berberin 0 , 1 % khdng thay s y xuat hign cua P.aeruginosa. S.aureus vd Aci.Baumanii, nhu-ng d nhdm d i p Silvirin 1 % v i n cdn 3 mdu du'ong tinh vdi P.aeruginosa, S.aureus vd Aci.baumanii.
3 100% BN phai p h i u thudt. Nhdm d i p kem Berbenn 0 , 1 % cd ty 1$ BN p h i u thudt l i l n ngay l l n dau cao ho-n nhdm d i p Silvinn 1 % (70% so vdi 53,3%). Trong so BN phai p h l u thudt Igi chu y l u Id ghdp da bo sung.
4. Md bgnh hpc tai chd VT cua ca hai nhdm nghidn cOu b i l u hidn: Tai chd VT t i l n triln t i t Idn theo thdi gian d nhdm d i p Berberin 0 , 1 % b i l u hidn rd rgt han so v * i nhdm d i p Silvirin 1 % : S6 lu-png t l bdo vidm giSm d i n vd s6 lu-png nguydn bdo spi tdng dan theo thdi gian.
TAI LI$U THAM K H A O
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