Danh gia doc tfnh ban triroiig dign cua bai thudc HA-02 tren dong vat thyc nghiem
Evaluating the Semi-Chronic Toxicity of HA-02 Remedy on Experimental Animals
Biii Thanh H a \ Nguyen Viit Trung", 'Benh vi$n 103. Hoc vien Quan Y Nguyen Tr9ng Tki" "Bgi hpc Ykhoa Vinh
Tdm t^t:
Muc tiiu: Nghien eUu tap trung danh g i i t i c ddng cua v i f c dpng v i t suf dung b i n trudng dien bai thudc HA-02 tdi tinh trang sUc khde, te b i o m i u , chufc n i n g gan t h i n . Ddi tugng vd phuang phdp: nghien cUu tien cUu mdt i c i t ngang cd ddi chUng thUc hien tren 20 chudt n h i t . Kit qud vd kit ludn:- Chudt udng lien tuc trong 30 ngay vdi lieu 54g/kg/ngiy, thudc HA-02 khdng gay thay doi vd sd lUpng hdng cau, bach cau, tieu cau, ham lupng Hemoglobin, hoat dp enzym SGOT va SGPT, ham lUpng Ure va Creatinin so vdi Id chu'ng cd y nghia thdng ke. Thude HA-02 eung khdng gay bien ddi ve md gan, than tren chudt nghien cUu.
TUkhda: ddc tinh ban trudng dien, chudt n h i t , HA-02
Summary:
Objective: This study was to evaluate the impacts of HA-02 on the health of animals, blood cells, liver and kidney functions.. Subject and method: A cross-sectional and case control study was conducted on 20 mice. Result and conclusion: The administration of HA-02 continuously for 30 days (54g/kg/day) on mice did not result in any significant change in the count of erythrocyte, leukocyte and platelet, hemoglobin concentration, SGOT and SGPT activities, urea, and creatinine levels between the treated group and the control group. Neither did HA-02 cause any histological change in the liver and kidney cells of animals.
Keywords: semi-ehronie toxicity, mice, HA-02.
I.Datvande lai t i n g , b e n h ' n h i n p h i i dCing t h u d c lien tuc, sudt ddt, ngoai ra thudc ed nhieu t i e d u n g p h u i n h Tang huyet ap (THA) la m d t benh t i m mach,
man t i n h , p h d bidn nhat tren the gidi v i la 1 t r o n g 6 ydu t d nguy co ehinh i n h h u d n g tdi phan b d g i n h nang b e n h tat t o i n c i u . Cac thude tay y dieu tri THA hien ed rat nhieu loai, t u y nhien phan Idn m d i chi dieu trj dupe trieu chUng, ngUng t h u d c t h i huyet ap
h u d n g den siJc khde ngudi benh. Do do t h u d c Y hpc ed truyen (YHCT) dang dupe quan tam nhieu vi day l i e i e thude it t i c d u n g p h u , ed t h e d u n g duac dai ngay phu h p p vdi didu t n THA.
ThUe hien p h u o n g c h i m ket h o p hai nen y hpc, Bd m d n Khoa YHCT- Benh vien 103 tren eo sd bien chufng luan tri t h e o ly luan eua YHCT vd nguyen Phan biln khoa h^c: PGS.TS. NGUYEN THANH BINH " ^ ^ " ' ' ' ^ *^^^ ^ ^ " ^ ^ ' " ^ "^^^ ' ^ ^ " ^ ^HA d d n g t h d i van 141
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d u n g ket q u i nghien cdu theo y hpc hien dai ve t i c d u n g dupe ly eua tUng vj thude da x i y d u n g bai thudc "HA-02" g d m 15 vi thude d d n g dUpc de dieu trj benh THA. Bai thudc cd t i e d u n g binh ean t i e m d u o n g , t u bd can than am, hoat huyet trU d i m va Ipi thuy. Chung tdi d i tien hanh xdc djnh ddc tfnh bdn trudng dien cOa thuoc HA-02 trin ddng vat thuc nghiim de cd so sd di sau t i m hieu t i c d u n g eda thudc HA-02.
2. Odi tuong va phuong phap nghien cuTu 2.7. Nguyen lieu nghien cihi
Thudc HA-02 dang djch chiet dUpc ed each thCiy den dp d i m d i e nhat cd t h e cho chudt udng dupe b i n g kim dau t u chuyen d u n g . Sau khi cd d i e nhat dupc cao dac ty le 2/1 ( I m l cao chu'a 2g dupe lieu), dCjng eao d i e de danh g i i ddc t i n h b i n t r u d n g dien tren d d n g v i t thuc nghiem. Tieu chuan dUpc lieu dupc xae djnh theo tieu ehuan dupe dien Viet nam IV, thudc dupc b i o che tai Xi nghiep dupe pham Trung UOng 1.
2.2. Ddi tugng nghien cdu
Chudt n h i t t r i n g : 20 con d d n g swiss, t r p n g lupng 20 ± 2g/con, dupc nudi t r o n g eung mdt dieu kien (nhiet dp mdi t r u d n g 25°C, dp am khdng khi 80-90% va eung mdt che do dinh dudng).
20 chudt 6ugc chia l i m 2 Id: 1 Id chu'ng va 1 Id thCr, mdi Id 10 eon.
+ Ld chUng: 10 eon, dupc u d n g nudc cat vdi lupng 0,1 ml/1 Og t h e t r p n g .
+ Ld thude: 10 eon, udng nUde s i c cd d i e eda bai thudc HA-02 vdi lieu t u o n g u'ng 54g dupe li$u khd/kg/ngay (tUong d u o n g 12 lan lieu d u n g t r u n g binh tren ngudi), tUOng Ung vdi t h e tfch 0 , l m l / 1 0 g t h e t r p n g .
Nude cat va thudc thCr dupc dUa v i o da day chudt b i n g kim cong dau t u v i o cae budi s i n g tU 8- 10 g i d , 1 lan/ngay t r o n g 30 ngay lien tue.
2.3. Cac chi tieu theo doi
•^ Tmh trang ehung: C i c chl sd ve can nang dupc e i n b i n g can dien xd, 1 lan/tuan. Cac chl sd ve
hanh v i , Idng, p h i n : dupe t h e o ddi -"^Q ^^^"^
hang ngay.
+ D i n h gia chUe nang tao m i u : t h d n g ^ q u a sd lupng h d n g cau, h i m lupng h e m o g l o b i n , sd lUpng bach cau v i sd lupng t i ^ u cau.
+ D i n h g i i chUc n i n g gan t h d n g qua djnh lUpng mdt sd enzym: SGOT, SGPT trong huydt thanh chudt.
-I-Dinh g i i chUc n i n g t h i n t h d n g qua djnh lUpng djnh lupng Ure, creatinin trong huyet thanh chudt.
+ M d benh hpe: Sau 30 ngay u d n g thudc, tidn hanh kiem tra n g i u nhien cau true vi t h d gan t h i n cOa 5 0 % sd c h u d t d m d i Id.
3. Ket q u ^
3.1. Tmh trang ehupt
Trong sudt t h d i gian t h i n g h i e m 30 ngay, tat c i chudt t h i n g h i e m d eac n h d m deu hoat d d n g binh t h u d n g , nhanh n h e n , i n u o n g t d t , phan khd, Idng mUpt, khdng cd c h u d t t h i n g h i e m bj chet h o i c cd eac bleu hien bat t h u d n g .
3.2, Trgng lugng cda cie 16 ehupt trong qui trinh thi nghiem
BSng 3 . 1 . Can nang chudt trUdc va sau t h i nghiem
Lo nghien cufu
ChuYig Thuoc
n
10 10 P chilng-thCf
Can nang (g) Tn/dcthf
nghiem 22,3 ±1,67
21,5 ± 1 , 4 p > 0,05
Sau thi nghiem 24,9 ±1,1 24,1 ± 0,97
p > 0,05
Nhdn xit:
Tai t h d i d i e m b i t dau t h i n g h i e m , ehupt cua hai Id cd t r p n g lUpng can b i n g nhau. Tai t h d i diem ket t h u c t h i n g h i e m , chudt eCia hai Id cd s u t a n g trpng k h o i n g 2-3 g / c o n , khdng cd sp khae biet ed y nghia t h d n g ke vd t r p n g l u p n g ehupt cua hai Id tai thdi d i e m n i y .
Tap 9-So 4/2014
01 20
I
--•Riu6cTuan 2 TuSn3 TijSn4 TuJn 5
chisd
Hong c i u(T/l)
Bach cau (G/l)
Hemoglobin (g/dl)
Tieu c$u (G/l)
Chung Thu6c
n 10 10
Trung binh ±SD 6,9±2,4 5,6±1,5 p >0,05 Chijfng
Thudc 10 10
7,9± 0,4 8,1 ±0,5 p>0,05 ChuTig Thudc
10 10
12,3±0,5 12,5±0,8 p>0,05 ChuYig Thuoc
10 10
822± 205 884±241 p>0,05
3.4. ChUc ning gan thin eua cac to ehupt sau khi ket thuc thi nghiem
BSng 3.3. Cic chl so sinh hoa mau ciia chuot sau thi nghiem
Hinh 3.1. Cdn ndng d chudt trong qud trinh thi nghiem
Trong sudt qui trinh thi nghiem, chudt d ci hai nhdm deu phit trien binh thudng vd trpng lupng.
Khdng cd sU khie biet cd y nghia thdng kd ve trpng lupng ehupt tai eac thdi diem danh gia.
3.3. Chi s6 huyet hgc eda cic Id ehupt sau khi ket thuc thi nghiim
BSng 3.2. Cic chi so huyet hoc cOa chuot sau thi nghiem
Chisd
Ure (mmol/l)
Creatinin (mmol/l)
SGOT (u/l)
SGPT (u/l) Chung Thudc
n 10 10
Trung binh +SD 6±2,3 6,8± 1,3 p>0,05 ChCing Thudc
10 10
38± 29,3 27,8± 4,2 p>0,05 Chu'ng
Thudc 10 10
26,37 24,4+ 7,7 p>0,05 Chijfng
Thudc 10 10
4 4 p>0,05
Nhan xit:
Tai thdi diem ket thiic thi nghiem, cic xet nghiem phin anh chCtc nSng gan v l than cho thay khong co strlnh hudng cCia thudc t6i chiJc nang hai CO quan nly thong qua chi tieu ndng do ure, creatinin, SGOT, SGPT. Khdng cd sU khIc biet ding ke giUa hai nhdm chijfng va nhdm thudc.
3.S. Hinh thai mo benh hpc gan, thAn cua cac Id chuot sau Ichi Icet thuc thi nghiem
Nhdn xit:
Sau 30 ngly udng thuoc HA-02, so luong bach cau, hong cau, tieu cau, hemoglobin khdng cd sU
khic biet tl 'ig ke giiia hai Id chijfng v l nhdm thudc. " ' " ' • ^-^^ ^'"^ ""^'"° *'?"'' ''PC gan chuot did chUng
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Hinh 3.3. Hinh anh md benh hoc gan chudt did thuoc Nhdn xit:
Hinh inh md hoe md gan: eac be gan sip xep thanh dii, eau trdc rd, cic te bio gan v i te bio ndi md Idt Idng cac xoang tinh mach cd cau true binh thudng; eau true khoing cOra binh thudng. Khdng phit hien thay hinh inh tdn thuong cCia eic miu quan sat tren ei hai Id chUng v i thude
Hinh 3.5. Hinh dnh mo binh hpc than chuot 616 thuoc
Nhdn xit:
Hinh i n h md hpe md t h i r -upn mach cQa cae tieu eau than cd cau trdc binh thUdng, eac te bio ndi md cCia cudn mach nhd va deu nhau.
Khoang Bowman rd. Cic td bao dng than deu nhau, rd cau true, eac te bio bieu md dng thin binh thudng. Khe than hep. Mao mach m i u thinh mdng, te bao ndi md rd. Khdng phit hien thiy hinh i n h benh ly.
4. Ban luan
Trong nghien cufu nay, dpc tinh ban trudng diln cijia bii thude HA-02 dupe nghidn cdXJ tren chudt nhit tring. Trong thdi gian thi nghidm 30 ngiy, tat ei cae ehupt 6 ei hai Id deu hoat ddng binh thudng, nhanh nhen, an udng tdt, phin khd, Idng mUpt, khdng thay bieu hien bd an, Idng rung. Chudt tang trpng, sU tang can d hai nhdm khdng cd sU khac biet ed y nghia thdng ke (p>0,05).
Cie ehi so huyet hpc nhu sd lupng hdng cau, ham lupng hemoglobin, sd lupng bach eau va sd lupng tieu cau deu khdng ed sU khac biet dang ke cd y nghia thdng ke (p>0,05) giOra hai Id chijfng va thude. Dieu nay cho thay thudc HA-02 khdng lam thay ddi cae thinh phan cua mau.
Khi theo ddi i n h hudng cOa thudc HA-02 tdi eac chi sd hda sinh phin anh chCfc nang gan, chung tdi thay sau udng thudc 30 ngiy, hoat dp cae enzym SOT, SGPT trong huyet thanh ehupt eda id thCr khdng cd sU khae biet cd y nghTa thdng ke so vdi Id chUng (p>0,05). Ddi vdi ehUe ning thin, cic chl sd Ure, creatinin trong huyet thanh chudt cung khdng khic biet giaa hai Id sau thi nghiem (p>0,05).
Hinh inh tieu bin md bdnh hpc gan eua eic Id ehupt sau thi nghiem, khdng phat hien thay hinh inh tdn thuong viem, xo hda. Tren tieu bin md benh hpc cCia than thiy rd eau true vung tuy, viJng v6, khoang Bowmann rd ciu trdc, eac tieu cau thin nd to tai cic cudn maeh d ei hai nhdm ehUng va nhdm nghien eUu.
Nhu vay qua nghien cu'u ehung tdi chua thay
thudc HA-02 giy doe tren dpng Vc r nghiem
T i p 9- S6 4 /2014
5. Ket Juan
Thudc HA-02 khdng gay ddc tren d d n g vat thuc nghiem. Tren chudt vdi l i l u 54g/kg/ngay (gap 12 lan lieu d u n g tr§n ngudi) u d n g lien tuc t r o n g 30 n g l y , thudc HA-02 khdng gay cac thay ddi cd y nghia thdng ke ve sd lugng h d n g cau, bach c i u , tieu cau, ham lifong Hemoglobin, hoat do enzym SGOT v l SGPT, h i m luong Ure v l Creatinin so vdi Id chu'ng.
Thudc HA-02 cung khdng gay bien ddi n i o ve cau true, te b i o m o gan va t h a n tren chuot nghien cu'u.
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