促肝细胞生长素对CCl4肝损伤小鼠的保护作用和机制研究

Study on Protective Effect and Mechanism of Hepatocyte Growth-promoting Factor on CCl4-induced Liver Injury in Mice

关键词:  促肝细胞生长素  肝损伤  Bcl-2  Bax

Key words:  hepatocyte growth-promoting factor  liver injury  Bcl-2  Bax

摘要:

目的 研究促肝细胞生长素(PHGF)对CCl₄肝损伤小鼠的保护作用和机制，为其临床应用提供理论依据。方法 小鼠灌胃CCl₄的植物油溶液80 mg·kg^-1建立肝损伤模型，连续尾静脉注射3个剂量的PHGF(12.5，25，50 mg·kg^-1)7 d后，取血清测定各组小鼠ALT和AST，T-SOD和MDA的值；取肝脏进行病理组织学检查；用Western blot法检测肝组织中Bcl-2与Bax蛋白的表达。结果 PHGF各给药组ALT与AST的值要明显低于模型组(P<0.05)，T-SOD和MDA值与肝损伤模型组比较差异不具有统计学意义；病理切片观察显示，各给药组的肝组织细胞坏死情况明显好于模型组；Western blot结果表明，PHGF各给药组的Bcl-2与Bax表达量的比值均明显高于模型组(P<0.01)，且具有一定的剂量依赖性。结论 PHGF对CCl4所致的小鼠肝损伤具有一定的保护作用，其作用机制可能与抗氧化作用无关，与其上调Bcl-2蛋白的表达并下调Bax蛋白的表达有关。

Abstract:

OBJECTIVE To study the protective effect and mechanism of hepatocyte growth-promoting factor(PHGF) on CCl₄-induced liver injury in mice and provide some theoretical basis for its clinical use. METHODS Liver injury model in mice was established by ig CCl₄(80 mg·kg^-1) and 3 doses of PHGF(12.5, 25, 50 mg·kg^-1) were administrated intravenously for 7 days. The ALT, AST, T-SOD and MDA levels of serum were detected and the liver tissues were observed histologically. The Bcl-2 and Bax protein expressions in liver tissue were detected using Western blot method. RESULTS The ALT and AST levels of each dose group of PHGF were significantly higher than those of the model group(P<0.05), but no significant differences of T-SOD and MDA levels could be found between model group and other groups. Through the pathological observation, each dose group of liver cell necrosis situation were obviously better than the model group. The administrated group, according high to low, the ratio of Bcl-2 and Bax increased significantly higher than the model group(P<0.01). CONCLUSION PHGF can protect the CCl4-induced liver injury in mice and the mechanism of action may have nothing to do with antioxidant effect but upregulation the expression of Bcl-2 protein and down expression of Bax protein.