基于保肝活性的大黄硝石汤组分配伍优化及药效评价

Compatibility Optimization of Dahuang Xiaoshi Decoction Components Based on Liver Protection and Evaluation of Its Efficacy

目的基于保肝活性优化大黄硝石汤组分配比,并进行药效评价。方法采用Wistar大鼠,随机分为空白组、模型组、熊去氧胆酸组(阳性组)及大黄硝石汤组分正交配伍组,采用α-萘异硫氰酸酯诱导肝损伤动物模型,以肝功能生化为指标,并结合多元统计方法,优化大黄硝石汤组分配比。另取Wistar大鼠,在肝损伤动物模型基础上,以生物体征、肝功能生化为指标,优化大黄硝石汤组分中芒硝剂量(0、1、2、4 g)。在此基础上,将Wistar大鼠随机分为空白组、模型组、熊去氧胆酸组,栀柏黄组分小、中、大剂量组,通过生物体征、肝功能生化、脂质过氧化物,肝脏病理及胆汁转运相关指标等考察,评价栀柏黄组分保肝药效。结果经正交、多元统计优化的大黄硝石汤组分能够改善肝损伤动物生物学体征及肝功能生化异常,含不同剂量芒硝的大黄硝石汤优化组分均能减缓肝损伤动物体质量减轻(P<0.01或P<0.05),降低血清肝功酶活性(P<0.01或P<0.05),且除碱性磷酸酶外,大黄硝石汤组分不同剂量芒硝组对肝功酶活性回调差异无统计学意义。综合考虑,将其组方优化为不加芒硝的栀柏黄组分。优化后的栀柏黄组分能改善肝损伤动物异常生物学体征,降低血清肝功酶活性(P<0.01或P<0.05)及总胆红素、三酰甘油水平(P<0.05),回调肝脏脂质过氧化物水平(P<0.01或P<0.05),修复肝脏病理,回调胆盐输出泵(BSEP)等胆汁转运蛋白表达(P<0.05),从而发挥较好保肝活性。结论经正交、多元优化及单因素考察得到的大黄硝石汤栀柏黄组分具有改善动物异常生物体征、保肝降酶、抗脂质过氧化、回调异常代谢、修复肝脏病理等药效,这为其进一步临床应用及开发提供了参考。

Objective To optimize the formula of Dahuang Xiaoshi decoction components based on its hepatoprotective activity and evaluate their efficacy.Methods The Wistar rats were randomly divided into blank group,model group,ursodeoxycholic acid group(positive group),and orthogonal groups of Dahuang Xiaoshi decoction components.The acute liver injury model induced by alpha-napthyl-i sothiocyanate(ANIT)was used to optimize the allocation ratio of Dahuang Xiaoshi decoction components by taking liver function indicators as an index and combining with multiple statistical methods.The additional Wistar rats were taken to induce liver injury and optimize the compatible dosage of Natrii Sulfas(0,1,2,4 g)in Dahuang Xiaoshi decoction components based on the biological signs and liver function biochemical indicators.On this basis,the Wistar rats were randomly divided into blank group,model group,ursodeoxycholic acid group and different dosages(low,medium and high)of the Zhibaihuang components group.The liver protective effect of Zhibaihuang components was systematically evaluated through the general biological signs,liver function biochemical indicators,lipid peroxide indicators,liver pathological examination and bile transport-related indicators.Results Dahuang Xiaoshi decoction components optimized by orthogonal and multiple statistics could improve the biological signs and ameliorate the biochemical abnormalities in rats with liver injury.Dahuang Xiaoshi decoction components combined with different dosages of Natrii Sulfas could slow down the mass loss of ANIT-induced acute liver injury rats(P<0.01 or P<0.05)and recall the abnormally elevated serum liver function enzyme activities(P<0.01 or P<0.05).Except for alkaline phosphatase(ALP),there was no statistical difference in regulating other liver function enzyme activity between different allocations of Natrii Sulfas.After comprehensive consideration,its composition was optimized to the Zhibaihuang components without Natrii Sulfas.Further pharmacodynamic evaluation results showed that the optimized Zhibaihuang components could improve their abnormal biological signs(P<0.01 or P<0.05),decrease the serum liver function enzyme activity(P<0.01 or P<0.05)and the levels of T-BiL and TG(P<0.05),and restore the levels of hepatic lipid peroxide(P<0.01 or P<0.05),repair liver pathological injury,adjust the expression of bile transport proteins(P<0.05),and thus exert good liver protective activity.Conclusion The optimized Dahuang Xiaoshi decoction components,Zhibaihuang components,was obtained through orthogonal,multiple statistics and univariate investigation.It could improve the abnormal biological signs of animals,protect the liver and reduce enzymes,resist lipid peroxidation,restore abnormal metabolic indicators,and repair liver pathological injury,which provides a reference for its further clinical application and development.