慈菇消脂丸对非酒精性脂肪性肝炎模型大鼠JNK1、p-c-Jun和Caspase-8表达的影响

Effects of Cigu Xiaozhi Pills on Expressions of JNK1, p-c-Jun and Caspase-8 in Non-alcoholic Steatohepatitis Model Rats

目的观察慈菇消脂丸对非酒精性脂肪性肝炎模型大鼠JNK1、p-c-Jun、Caspase-8表达的影响,探讨其相关作用机制。方法实验大鼠随机分为正常组、模型组、阳性对照组和慈菇消脂丸高、中、低剂量组,每组10只。采用高脂饲料喂养大鼠制作非酒精性脂肪性肝炎模型大鼠,造模同时给予相应药物干预。造模12周后处死全部大鼠,取出肝脏。电镜观察肝细胞超微结构,TUNEL法检测肝细胞凋亡,qRT-PCR和Western blot分别检测肝组织JNK1、p-c-Jun、Caspase-8 mRNA和蛋白的表达。结果电镜观察显示,模型组大鼠肝细胞肿胀呈气球样变,胞浆中布满众多大小不一的脂滴。与正常组比较,模型组大鼠肝细胞凋亡显著增加,JNK1、p-c-Jun、Caspase-8 mRNA和蛋白表达显著升高;与模型组比较,慈菇消脂丸各剂量组和阳性对照组大鼠肝细胞脂肪样变显著减少,细胞凋亡显著下降,JNK1、p-c-Jun、Caspase-8 mRNA和蛋白表达显著降低。结论慈菇消脂丸通过调节JNK信号通路抑制肝细胞凋亡,对非酒精性脂肪性肝炎模型大鼠有一定的治疗作用。

Objective To observe the effects of Cigu Xiaozhi Pills on the expressions of JNK1,p-c-Jun and Caspase-8 in non-alcoholic steatohepatitis(NASH)model rats;To discuss its related mechanism of action.Methods Totally sixty SPF grade male SD rats were divided into six groups randomly:normal control group,model group,positive medicine group,Cigu Xiaozhi Pills high-,medium-and low-dosage groups,with 10 rats in each group.NASH model was established by feeding rats with high fat diet.At the same time,the model rats were given medicine intervention.At the end of 12 weeks,all the experimental rats were killed and the livers were taken.The ultrastructure of liver cells was observed by transmission electron microscope.Hepatocyte apoptosis was detected by TUNEL method.The expressions of JNK1,p-c-Jun,Caspase-8 mRNA and protein in liver tissue were detected by qRT-PCR and Western blot.Results Under electron microscope,the liver cells in the model group were swollen in balloon shape,and the cytoplasm was covered with numerous fat droplets of different sizes.Compared with the normal group,the apoptosis of hepatocytes significantly increased,and the expressions of JNK1,p-c-Jun,Caspase-8 mRNA and protein significantly increased in the model group.Compared with the model group,the adipose samples of hepatocytes in each Cigu Xiaozhi Pills group and positive medicine group decreased significantly;the apoptosis rate decreased significantly;the expressions of JNK1,p-c-Jun,Caspase-8 mRNA and protein decreased significantly.Conclusion Cigu Xiaozhi Pills can inhibit hepatocyte apoptosis by regulating the JNK signal pathway and play a therapeutic role in NASH.