作者:马小娟, 颉东升, 何国梁
【摘要】 目的观察加味茵陈五苓散对免疫性肝损伤的保护作用以阐明其药效和药物作用机理。方法采用卡介苗(BCG)+脂多糖(LPS)诱导小鼠免疫性肝损伤模型,观察本方对肝损伤小鼠血清谷丙转氨酶(ALT)及谷草转氨酶(AST)活性,脾、肝脏器系数,肝脏病理组织学损伤程度的影响,并检测小鼠肝组织匀浆丙二醛(MDA)、超氧化物歧化酶(SOD)的含量,血清一氧化氮(NO)含量及肿瘤坏死因子(TNF-α)的含量。结果加味茵陈五苓散和阳性对照药物五酯片均能显著降低BCG/LPS免疫性肝损伤小鼠血清中升高的ALT、AST水平;且加味茵陈五苓散中剂量降酶作用优于阳性对照组;对肝脾重量的增大有显著的抑制作用;组织病理检查结果显示本品中、高剂量可减轻肝组织坏死范围及程度,减少炎细胞浸润,有明显的保肝作用。同时发现中剂量药物可显著降低肝匀浆中升高的MDA水平,提高肝匀浆 SOD水平,显著降低血清中升高的NO含量和TNF-α含量。结论加味茵陈五苓散对免疫性肝损伤具有保护作用,其机制可能与其直接清除自由基、降低脂质过氧化物水平、提高SOD活性、减少炎性细胞因子的产生和调节机体免疫功能等有关。
【关键词】 加味茵陈五苓散; 卡介苗(BCG); 脂多糖(LPS); 免疫性肝损伤
Abstract:Objective To study the effects of Modified YinChenWuLingSan on immunological liver injury in mice induced by BCG+LPS and its mechanism. MethodsModified YinChenWuLingSan was given to the model mice with immunological liver injury induced by BCG+LPS.The samples of blood and liver were measured. The serum activities of ALT and AST were analyzed, organ(1iver,spleen) immunological indexes were measured and the pathological change of hepate was observed.The content of MDA and the activity of SOD in liver homogenate were measured.The content of NO and TNF-α in serum were measured also.ResultsModified YinChenWuLingSan and WuZhi pill all could significantly decrease serum ALT and AST activities of model mice ,and Modified YinChenWuLingSan medium dosage had better effect than WuZhipill.Modified YinchenWulingSan was also found to inhibit the enlargerment of liver and spleen,reduce the putrescence of hepatic cell,decreased MDA content and SOD activity in liver homogenate,and reduce the levels of NO and TNF-α in serum obviously.ConclusionModified YinchenWulingSan can prevent liver damage induced by BCG and LPS in mice by scavenging oxygen free radical,inhibiting lipid peroxidation and regulating immune function.
Key words:Modified YinChenWuLingSan/pharmacodynamic; Bacillus of Calmette-Guefinvaccine; Lipopolysaccharide; Immune hepatic injury
加味茵陈五苓散为经方茵陈五苓散加减化裁而成,具体药物由茵陈30 g,泽泻15 g,茯苓15 g,猪苓15 g,白术15 g,白背叶根30 g,叶下珠20 g(又名:珍珠草)、黄花倒水莲15 g组成,即由茵陈五苓散去辛温之桂枝,加入近年来治疗肝炎临床疗效显著的中草药白背叶根、叶下珠(珍珠草)、黄花倒水莲而组成的,全方具有清热利湿,益气健脾,活血化瘀的作用,本复方临床主要用于治疗病毒性肝炎、酒精性肝炎及肝纤维化等肝病,在改善患者肝功能和临床症状方面疗效确切。
现代研究表明,免疫损害机制在病毒性肝炎尤其是乙型肝炎发病过程中起主要作用。本实验在中医理论指导下,基于以上的研究基础,以卡介苗 (BCG)+脂多糖(LPS)所致免疫性肝损伤小鼠为研究对象,观察加味茵陈五苓散对免疫性肝损伤的保护作用,并初步探讨该方防治肝损伤的作用机理,从而为加味茵陈五苓散治疗病毒性肝炎提供实验依据,也为该方的进一步研究打下基础。