慈菇消脂丸对非酒精性脂肪肝炎大鼠肝组织脂质过氧化与TNF-α表达的影响

Cigu Xiaozhi pills′s influence on lipid peroxidation and TNF-α expression in liver tissues of rats with nonalcoholic steatohepatitis

目的:研究中药慈菇消脂丸对大鼠非酒精性脂肪肝炎(NASH)肿瘤坏死因子α(TNF-α)表达的影响。方法:50只雄性SD大鼠随机分为正常组(n=10)、模型组(n=10)、慈菇消脂丸高剂量组(n=10)、慈菇消脂丸低剂量组(n=10)、东宝肝泰阳性药物对照组(n=10),正常对照组给予基础饲料,其余4组建立非酒精性脂肪肝炎大鼠模型,同时给予中药和阳性药物干预。实验结束后处死大鼠取出肝组织,观察肝组织病理形态学的变化,测定血清甘油三酯(TG)、总胆固醇(TC)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、和肝匀浆丙二醛(MDA)、超氧化物歧化酶(SOD)、谷光苷肽过氧化物酶(GPX)。分别用免疫组化技术和RT-PCR法检测肿瘤坏死因子α(TNF-α)在肝脏的表达。结果:模型组大鼠肝组织出现脂肪变性及不同程度的炎性细胞浸润,镜下可见肝细胞内大量脂滴。中药治疗组及阳性药物对照组大鼠脂肪性肝炎明显减轻。与模型组比较,中药治疗组和阳性药物对照组大鼠血清TG,TC,ALT,AST和肝脏MDA明显降低,而SOD,GPX活性明显增加。正常组大鼠肝组织内几乎无TNF-αmRNA和蛋白表达。与正常组相比,模型组TNF-αmRNA及蛋白表达显著增加(P<0.05)。与模型组比较,中药治疗组及阳性药组大鼠肝组织内TNF-αmRNA和蛋白表达显著降低,差异具有统计学意义(P<0.05);且中药高剂量治疗组作用较阳性药组显著(P<0.05)。结论:TNF-α在大鼠非酒精性脂肪肝炎中发挥着重要作用,慈菇消脂丸对大鼠非酒精性脂肪肝炎具有明显的防治作用,其作用机制可能与改善肝组织脂肪变性程度、抑制脂质过氧化、抗炎有关。

Objective： To investigate the effect of Cigu Xiaozhi pills on expression of tumor necrosis factor α（TNF-α） in rat with nonalcoholic steatoheptatitis（NASH）.Method： Fifty male SD rats were divided randomly into five groups： the normal group（n=10）,the model group（n=10）,the high dosage group（n=10）and the little dosage group of the treatment（n=10）,Dongbao Gantai group（n=10）.Rats in normal control group were fed with standard diet.Rats in other four groups were established models of nonalcoholic steatohepatitis and were treated simultaneously with traditional Chinese medicine and positive medicine.Histopathological changes in the liver were observed.The serum ALT,AST,TG,TC and hepatic MDA,SOD,GPX were detected histologically.The expression of TNF-α in the liver was determined using the immunohistochemical technique and RT-PCR.Result： In model group,extensive adipose degeneration and inflammatory cell infiltration were found in the liver.In treatment groups steatohepatitis were markedly alleviated.Compared with model group,TG,TC,ALT,AST of the serum and MDA of liver tissue were reduced significantly,and SOD,GPX were increased significantly in treatment groups and positive control group（P0.05）.TNF-α was not expressed almost in normal rat liver and was expressed highly in model rat liver.Compared with model group,the TNF-α mRNA and protein expression were significantly lower in liver of treatment groups and positive control group（P0.05）.And the effects of high dosage group surpass than those of Dongbao Gantai group（P0.05）.Conclusion： TNF-α plays an important role in NASH pathogenesis.Cigu Xiaozhi pills can effectively treat experimental nonalcoholic steatohepatitis in rats,and its mechanism may be associated with ameliorating hepatocellular steatosis,removing the free radicals and enhancing the capability of anti-oxidation and anti-inflammatory.