抗TNF抗体和谷胱甘肽对大鼠脂肪肝的防治作用研究

The effect of monoclonal antibody of tumor necrosis factor-α and glutathione on rat fat liver experimental models

目的用抗TNFα单克隆抗体(TNFαMcAb)和还原型谷胱甘肽(GSH)药物治疗酒精性与营养性肥胖模型大鼠,观察两种药物的疗效。方法分别建立酒精性与营养性肥胖大鼠实验动物模型,设立TNFαMcAb和GSH预防组、治疗组和停灌酒或高脂饲料的对照组,光镜和电镜观察大鼠肝组织病理改变,比较各组间大鼠内毒素水平,肝功能和血糖血脂变化情况。结果各组大鼠经抗TNFαMcAb与GSH预防性治疗或治疗4周后血清内毒素水平均有不同程度下降,肝功酶学水平亦随之下降,与自身前期相比差异显著(P<0.05);经GSH治疗的两肥胖模型组血总胆固醇水平有所下降,与实验对照组相比有显著差异(P<0.05);肝组织炎症活动度减轻。预防组疗效优于治疗组。结论抗TNFαMcAb和GSH可促进肝脏功能恢复,在酒精性和非酒精性肝损伤早期应用有明显保护作用。

Objective To investigate the effect of the two medicines, monoclonal antibody of tumor necrosis factor-α （anti-TNFet Acb）and glutathione （GSH）, which were used to treat the rat ALD and NALD experimental models. Method Rats were randomly allocated into ALD and NALD experimental or control groups, anti-TNFα McAb and GSH prevention or treatment groups of ALD or NALD,respectively. Rat liver tissues were observed before and after 4 weeks prevention or treatment to assess the effect. Blood samples were collected for measuring the liver function, blood total cholesterol, serum triglyceride and blood glucose. Liver tissue was obtained for pathological test by HE and electron microscopy. Results The endotoxin level of each group decreased in various degrees after 4 weeks treatment with anti-TNFα McAb and GSH. The liver functions of rats in the two model groups were abnormal. Serum aminotransferase was apparent decreased after treatment. Serum total cholesterol level decreased in nonalcoholic liver disease group after treatment by GSH. There was a statistically significant difference （P 〈 0.05） when compared with that of control groups. But the blood glucose level was similiar. At the same time, the inflammatory cell infiltration and necrosis was recovered in models with alcoholic and nonalcoholic liver disease after treatment of CSH. The curative effect of preventive groups was better than that of treatment groups. Conclusions Anti-TNFα McAb and GSH might decrease the level of endotoxin and have benefit in recovery of liver function and could reverse or prevent the occurrence of hepatocytes lesion in ALD and NALD experimental rat models.