雷帕霉素调节基质金属蛋白抑制大鼠肝纤维化的相关性研究

Correlation study of rapamycin adjusting metal matrix proteins on inhibition of hepatic fibrosis in rats

[目的]观察雷帕霉素(RAPA)对肝纤维化模型大鼠肝组织内基质金属蛋白MMP-2,MMP-13表达水平的影响,探讨RAPA抑制大鼠肝纤维化的作用机制.[方法]将实验大鼠随机分为正常对照组、模型对照组及RAPA干预组.以四氯化碳花生油构建大鼠肝纤维化模型,RAPA干预组于实验第6周灌胃给予2mg/kg RAPA,每日1次,持续2周.应用光学显微镜观察肝纤维化情况,免疫组织化学方法观察模型对照组和RAPA干预组MMP-2,MMP-13蛋白表达水平.[结果]常规染色切片观察结果显示,模型对照组肝组织呈混合性脂肪变性,细胞体积明显增大,纤维间隔明显增生,成纤维细胞及炎症细胞增生浸润;RAPA干预组肝纤维化程度较模型对照组明显减轻,组织结构清晰.免疫组织化学观察结果显示,与模型对照组比较,RAPA干预组MMP-13蛋白表达明显增高(P<0.05),而MMP-2蛋白表达明显下降(P<0.05).[结论]RAPA通过上调肝组织中MMP-13表达及下调MMP-2表达从而缓解肝纤维化进展.

OBJECTIVE To observe the effects of rapamycin（RAPA）on expression of matrix metal MMP-2,MMP-13 in hepatic fibrosis models of rats,and to study the mechanism of inhibitory effect of RAPA on hepatic fibrosis in rats.METHODSExperiment rats were randomly divided into groups of control,model and RAPA intervention.Liver fibrosis model of rats were established by peanut oil of CCl4,and the rats in RAPA intervention group were given 2mg/kg of RAPA by gavage,once a day for two weeks.Liver fibrosis was observed by light microscope,and expression of MMP-2and MMP-13 protein expressions in model group and RAPA intervention group were observed by immunohistochemistry.RESULTSIt was observed in liver fibrosis model group that fatty degeneration of hepatocytes,significant increase of cell volume and hyperplasia of fibrous septa and fibroblasts,and infiltration of inflammatory cells.The degree of liver fibrosis in RAPA intervention group was significantly alleviated than that in liver fibrosis model group,and organizational structure was clear.The expressions of MMP-13 and MMP-2 were significantly higher and lower in the RAPA intervention group than in the model group,respectively（P〈0.05）.CONCLUSION RAPA intervention alleviates the progress of liver fibrosis by upregulated the expression of MMP-13 and downregulated the expression MMP-2 in liver tissues.