大承气汤对急性肝衰竭大鼠FADD介导的肝细胞凋亡作用研究

Experimental Study on Intervention of Dachengqi Tang for Liver Apoptosis Induced FADD in Acute Hepatic Failure Rats

摘要:

目的: 研究大承气汤对急性肝衰竭大鼠Fas相关死亡结构域蛋白(FADD)介导肝细胞凋亡的干预作用。方法: 40只大鼠随机分为4组,分为正常对照组(A组),急性肝衰竭造模组(B组),大承气汤低剂量治疗组(C组),大承气汤高剂量治疗组(D组),每组各10只。C,D组大鼠于造模前2 d分别灌胃不同剂量大承气汤2 mL,A,B组予同等剂量生理盐水灌胃,继而B,C,D组大鼠均采用皮下注射硫代乙酰胺完成急性肝衰竭动物模型,造模完成后继续予药物灌胃3 d,处死所有大鼠,进行肿瘤坏死因子测定,进行肝脏病理学,FADD,肿瘤坏死因子受体1(TNFR1),Caspase-8免疫组化及肝脏组织细胞凋亡检测。结果: 硫代乙酰胺可引起急性肝衰竭并有广泛的肝细胞凋亡,同时可见FADD,TNFR1,Caspase-8蛋白在肝细胞中强表达;与模型组比较,大承气汤各组肝组织衰竭减轻,肝细胞凋亡率降低,肿瘤坏死因子-α(TNF-α)含量下降,FADD,TNFR1,Caspase-8在肝细胞中的表达降低。高剂量组治疗效果更好。结论: 大承气汤可防治肝细胞凋亡,其作用机制可能与抑制FADD介导的肝细胞凋亡有关。

Abstract:

Objective: To explore the effect of Dachengqi tang on liver apoptosis induced Fas-associated death domain (FADD) in acute hepatic failure rats. Method: Forty Wistar rats were randomLy divided into 4 groups:normal group(group A), model group(group B),treatment group of Dachengqi tang at low dose(group C), treatment group at high dose(group D).There were 10 rats in every group. The level of tumor necrosis factor-α(TNF-α) was measured,Hepatic FADD,tumor necrosis factor receptor type 1(TNFR1) and Caspase-8 activities were examined,liver cell apoptosis was observed.Liver pathology was observed. Result: Thioacetamide (TAA) could induce acute hepatic failure,with extensive liver apoptosis, the expression of FADD,TNFR1 and Caspase-8 were significantly increased in TAA model group.Compared with group B.the percentage of liver cell apoptosis was decreased in C,D groups, the pathology change of liver was decreased in C,D groups,the level of TNF-α was decreased in C,D groups.The expression of FADD,TNFR1 and Caspase-8 were decreased in C,D groups. Conclusion: Dachengqi tang can prevent and cure liver apoptosis, it may be related to depress rhe liver apoptosis induced FADD.