解毒化瘀Ⅱ方对暴发性肝衰竭大鼠TNF-α/TNFR1及Fas/FasL表达的影响  

Effect of Detoxification and Dissipation Blood Stasis Formula II on expression of TNF-α/TNFR1 and Fas/FasL in rats with fulminant hepatic failure

作　　者：毛德文[1] 邱华[1] 刘洁[1] 农朝赞[1] 黄古叶[1] 

机构地区：[1]广西中医学院第一附属医院中医肝病治疗中心,广西南宁530023

出　　处：《中医药学报》2007年第1期13-16,共4页Acta Chinese Medicine and Pharmacology

基　　金：国家自然科学基金(No.30360125);广西自然科学基金(No.桂科自0542103)

摘　　要：目的:研究解毒化瘀Ⅱ方对暴发性肝衰竭大鼠TNF-α/TNFR1及Fas/FasL表达的影响。方法:SPF级Wistar大鼠84只,随机分为空白组、模型组、解毒化瘀Ⅱ方低、中、高剂量组、安宫牛黄丸组、乳果糖组,以硫代乙酰胺(TAA)皮下注射复制急性肝衰竭大鼠模型,造模前3d开始灌胃给药,2次/d,间隔12h,共给药5.5d;采用ELISA法检测各组大鼠血清中TNF-α含量,Western blot法测定肝细胞TNFR1的表达量,免疫组化法检测Fas/FasL在各组肝细胞中分布的趋势及表达强度。结果:与空白组比较,模型组大鼠血清中TNF-α含量升高,肝细胞TNFR1、Fas、FasL的表达均显著增强,差异有统计学意义(P<0.01),解毒化瘀Ⅱ方能降低血清TNF-α的含量,抑制肝细胞TNFR1、Fas/FasL的表达,呈现量效关系,并以解毒化瘀Ⅱ方高剂量组作用效果最佳。结论:解毒化瘀Ⅱ方抗肝衰竭的作用机制可能是通过干预TNF-α/TNFR1及Fas/FasL的表达,阻止死亡信号的转导,抑制肝细胞凋亡。Objective: To investigate the effect of Detoxification and Dissipation Blood Stasis Formula II on the expression of TNF-α/TNFR1 and Fas/FasL in rats with fulminant hepatic failure,and explore its mechanism of resisting hepatic failure.Methods: The rat models of fulminant hepatic failure were induced by hypodermic injection of thioacetamide(TAA).Eighty four Wistar rats of SPF grade were randomly divided into seven groups: blank group,model group,low dose group, medium dose group,high dose group,group of lactulose treatment and group of Angong Niuhuang Bolus treatment.Administration by gastric infusion was started 3 days before the model-making,twice daily with an interval of 12 hours,5 days in total.The level of TNF-α in serum was tested with ELISA,while the expression of TNFR1 protein in hepatocyte was detected with Western Blot,and the distribution and expression of Fas/FasL in hepatocyte were determined with immunohistochemistry.Result: Compared with blank group,the level of TNF-α in the serum and the expression of TNFR1 and Fas/FasL in hepatocyte of the model group significantly increased(P<0.01).Detoxification and Dissipation Blood Stasis Formula II reduced the level of TNF-α in serum and the expression of TNFR1、Fas/FasL in hepatocyte.There was also a dose-effect relationship between them,and the high dose group showed the best effect.Conclusions: The acting mechanism of Detoxification and Dissipation Blood Stasis Formula II to protect hepatocyte from Fulminant hepatic failure may be on the basis of interfering the expression of TNF-α/TNFR1 and Fas/FasL,interrupting the transduction of dead signal and inhibiting the abnormal apoptosis of hepatic cells.

关 键 词：暴发性肝衰竭 TNF-α/TNFR1 FAS/FASL 信号转导 解毒化瘀Ⅱ方 

分 类 号：R575.3[医药卫生—消化系统]