活血化瘀类方抗肝纤维化疗效比较

Compare the effects of traditional Chinese prescriptions formulae for promoting blood circulation on liver fibrosis induced by DMN in rats

目的:基于方证相对原理,通过肝肾纤维化方证数据库筛选分析,选择膈下逐瘀汤、复肝丸、燮枢汤、鳖甲丸4首方剂,观察他们对二甲基亚硝胺(DMN)大鼠肝纤维化的药效作用。方法:大鼠随机分为正常组、模型组、膈下逐瘀汤组、复肝丸组、燮枢汤组、鳖甲丸组和N-乙酰半胱氨酸对照药组。除正常组外,各组大鼠均以DMN 10μg/kg腹腔注射,每天1次,每周连续3天,共4周。造模第3周开始给予相应药物灌胃:膈下逐瘀汤7.03g/kg、复肝丸6.43g/kg、燮枢汤12.51g/kg、鳖甲丸5.40g/kg,正常组与模型组给予等体积的生理盐水灌胃,每天1次,连续4周。试剂盒测定血清ALT、AST、γ-GT活性及Alb、T.Bil含量,盐酸水解法测定肝组织羟脯氨酸(Hyp)含量,HE染色与天狼猩红染色观察肝组织炎症与胶原沉积情况。结果:与正常组比较,模型组大鼠体重明显降低,脾体比升高,腹水形成;血清ALT、AST、Tbil及肝组织Hyp含量明显升高,血清Alb明显降低;肝组织病理染色可见大量炎性细胞浸润、胶原纤维沉积明显,纤维间隔、部分假小叶形成。与模型组比较,复肝丸组、N-乙酰半胱氨酸组脾体比和ALT、Hyp含量等显著降低,肝细胞变性和炎症坏死明显减轻,胶原沉积明显减少,AST、Tbil、γ-GT无明显变化;膈下逐瘀汤组脾体比、ALT、Hyp含量等降低,但死亡率较高,肝组织病理炎症及纤维化程度均较重;燮枢汤组脾体比降低,其余指标无明显变化;鳖甲丸组脾体比降低,ALT、Hyp含量有所降低,但肝细胞变性、炎症坏死和胶原沉积无明显变化;结论:与N-乙酰半胱氨酸相似,复肝丸有较好的抗DMN大鼠肝纤维化作用。

Gexiazhuyutang （膈下逐瘀汤, GXZYT）, Fuganwan （复肝丸, FGW）, Biejiawan （鳖甲丸, BJW） and Xieshutang（燮枢汤, XST） are traditional Chinese prescriptions with the effect of promoting blood circulation. Based on documentary analysis, clinical practice and expert experience, these prescriptions may have the effect of anti-fibrosis. This study is to compare the effects of these prescriptions on liver fibrosis in rats induced by DMN and find the best one for new drug research and development. Methods ： Liver fibrosis was induced by DMN intraperitoneal injection 3 times every week for 4 weeks at a dose of 10mg/kg body weight in rats. The 105 male Wistar rats were ran- domly divided into 7 groups ： normal, model, GXZY, FGW, BJW, XST and NAC groups. The NAC is setted as positive control group. The latter five groups were administered with the extract of GXZYT, FGW, BJW, XST and NAC respectively, from the third week to the sixth. At the same time ,the normal and the model groups were given the same volume of pured water. The levels of serum alanine aminotransferase （ ALT）, aspartate aminotransferase （ AST）, total bilirubin （ T-Bil）, albumin （Alb） and -glutamyl transpeptidase （~,-GT） were asssyed by chemilumiescence. The hepatic collagen deposition was evaluated with Sirius red staining. The inflammation of the hepatic ceils was evaluated with H＆E. The hydroxyproline （Hyp） content was detected by acid hydrolysis method. Result：Compared with normal group, the levels of ser- um ALT, ALB, the HYP content in liver tissue and the deposition of hepatic collagen are statistical significanced in model group. Compared wfth model group, serum ALT, Hyp content and the fibrosis scores , H＆E were statistical significanced in FGW, NAC groups. There was no significanced changes in GXZYT , BJW, XST groups. Conelusion：FGW has the better effects on anti-liver fibrosis in rats induced by DMN among the four prescriptions.