高脂饮食实验性大鼠非酒精性脂肪性肝炎(NASH)进展过程TIMP表达与肝纤维化的关系

TO INVESTIGATE THE RELATION BETWEEN THE TIMP、MMP EXPRESSION OF LIVER AND HEPATIC FIBROSIS IN EXPERIMANTAL RATS OF NASH

目的通过高脂饮食制作非酒精性指肪性肝炎(NASH)动物模型,观察高脂饮食(NASH)大鼠TIMP、MMP表达与肝纤维化的关系。方法24只雄性SD大鼠随机分为正常饮食对照组(8只)、高脂饮食模型组(16只),实验时间16周,RT-PCR法检测TIMP-1、TIMP-2、MMP13mRNA的表达,放免法检测HA,Ⅰ型胶原免疫组化染色观察组织学改变。结果与正常组比较,高脂饮食大鼠IMP-1、TIMP-2、表达显著上升(P<0.05),HA水平明显升高,继续给予高脂饮食16W TIMP-1、TIMP-2表达水平进一步增高,同时Ⅰ型胶原沉积明显增多,MMP13表达也有一定的升高,与对照组比较无显著性的差异(P>0.05)。结论高脂饮食成功复制了(NASH)动物模型,NASH时TIMP表达上调,进一步加剧了肝脏的病理改变,促进了肝纤维化的发生。

Objective To duplicate nonalcoholic steatohepatitis（NASH） animal models by high fat diet. To investigate the relation between the TIMP ,MMP expression of fiver and hepatic fibrosis in experimental rats of NASH. Methods All rats were randomly divided into control group and model group. High fat diet was managed to duplicate NASH models for 16 weeks. HA was measured by radio immunity method. The expression of TIMP-1 ,TIMP-2,MMP13 was detected by RT-PCR. Immunohistochemical stain was used to analyze collagen I and histology of liver. Results The expression of TIMP-1 ,TIMP-2 was increased by high fat diet compare with control group （P 〈 0. 05 ） , further expression of TIMP-1 ,TIMP-2 was found in model group by keeping high fat diet. There was an obvious increase of HA while sedimentation of collagen I increased in model group. The expression of MMP13 was not significantly different in comparison with control group. Conclusion NASH rat models are duplicated by high fat diet successfully. The expression of TIMP is up-regulated in NASH rats and promote the progress of rat liver fibrosis.