摘要
目的:观察大鼠非酒精性脂肪肝模型肝组织纤维化形成过程中基质金属蛋白酶-13(MMP-13)和基质金属蛋白酶抑制物-1(TIMP-1)表达的变化,探讨其在非酒精性脂肪肝纤维化发生发展机制中的意义. 方法:SD大鼠40只,随机分为模型组和对照组,模型组大鼠通过高脂饮食制备高脂血症性脂肪肝模型, 并在20 wk、22 wk分批处死,采用半定量逆转录聚合酶链反应(RT—PCR)检测肝组织MMP-13mRNA和TIMP-1 mRNA的表达,并与肝脏组织学改变进行对照研究. 结果:模型组肝组织出现明显的脂肪变性及炎症坏死并伴有程度不同的纤维化,部分大鼠出现早期肝硬化.在20 wk肝组织MMP-13mRNA表达,模型组(1.14±0.29)明显高于正常对照组(0.71±0.08),有显著性差异(t=3.71,P<0.01)而TIMP-1mRNA表达,模型组(0.73±0.16)虽高于正常组(0.60±0.03),但差异无显著性.在22 wk MMP-13mRNA模型组(0.84±0.10)表达明显下降,而TIMP-1mRNA模型组(0.75±0.12) 表达则显著高于正常对照组(0.60±0.10),(t=3.13, P<0.01).肝组织HE和Masson染色提示肝脂肪变性和纤维化改变. 结论:非酒精性脂肪肝炎,随着纤维化进程MMP- 1.3mRNA表达由强到弱,TIMP-1mRNA表达逐渐增强,提示其可能参与非酒精性脂肪肝炎纤维化的机制.
AIM: To investigate the implications of matrix metallopro-teinase-13 (MMP-13) and tissue inhibitors of metallopro-teinase-1 (TIMP-1) in the development of liver fibrosis in experimental nonalcoholic steatohepatitis (NASH). METHODS: Sprague-Dawley (S-D) rats were randomly allocated into the normal group and the model group. NASH model was established by feeding rats with fat-rich diet; other rats fed with normal diet were taken as controls. All the rats were sacrificed at the 20th and 22nd week. The expression levels of MMP-13 and TIMP-1 were assayed by semi-quantitative RT-PCR. Conventional histological examinations of all the rats were performed after HE and Masson staining. RESULTS: At the 20th week, hepatic MMP-13 mRNA expression (1.14 ± 0.29) was increased in the model group compared with the normal group (0.71 ± 0.08, P<0.01). TIMP-1 mRNA level was also increased in the model rats, but the difference between the two groups (0.73 ± 0.16 vs 0.60 ± 0.03) was not statistically significant. At the 22nd week, MMP-13 mRNA expression was remarkably de- creased (0.84 ± 0.10), whereas TIMP-1 mRNA expression was significantly increased compared with the control group (0.75 ±0.12 vs0.60±0.10, P<0.01). Remarkable steatosis and fribrosis were also revealed by HE and Masson staining. CONCLUSION: Although MMP-13 expression is increased transiently in the early stage of NASH, TIMP-1 expression is enhanced continuously. The latter may inhibit MMP-13-induced collagen degradation, resulting in collagen accumulation in the liver. These data suggest that TIMP-1 plays an important role in the pathogenesis of NASH with liver fibrosis.
出处
《世界华人消化杂志》
CAS
北大核心
2005年第4期512-515,共4页
World Chinese Journal of Digestology
基金
上海市自然科学基金资助项目
No.03ZR14045~~
