细胞外信号调节激酶与胶原在肝纤维化过程中的表达及相关性

Expression of extracellular signal-regulated kinase in hepatic fibrosis and its correlation with collagen type Ⅰ and Ⅲ

目的:观察细胞外信号调节激酶(ERK)在肝纤维化组织中的表达变化及其与Ⅰ、Ⅲ型胶原表达的相关性,并探讨其在肝纤维化发生中的作用.方法:二甲基亚硝胺(DMN)诱导大鼠肝纤维化,于用药1、2、3wk分别取肝组织;收集临床肝手术标本,包括纤维化肝组织和远癌的纤维化肝组织,以正常肝组织做对照.采用免疫组化法检测ERK在肝纤维化组织中表达和定位及其与Ⅰ、Ⅲ型胶原表达的相关性.结果:随着大鼠注射DMN时间的延长,ERK、Ⅰ、Ⅲ型胶原的表达逐渐增加,且在各时间组肝组织中ERK的表达与Ⅰ、Ⅲ型胶原的表达呈正相关(1wk:r=0.75,0.68,P<0.05;2wk:r=0.82,0.78,P<0.05;3wk:r=0.74,0.83,P<0.05).同样,ERK在人肝纤维化组较对照组表达增加(1.068±0.258vs0.035±0.011,P<0.05),且ERK的表达与Ⅰ、Ⅲ型胶原的表达正相关(r=0.87,0.88,均P<0.05).结论:ERK可能与肝纤维化的发生机制及胶原合成密切相关.

AIM： To investigate the expression of ERK during the development of hepatic fibrosis and the correlation of ERK and I, Ⅲ collagens. METHODS： Hepatic fibrosis was induced by subcutaneous injection of DMN. Rats were killed for study at the end of first, second, third weeks and the clinical operative liver samples were col-lected. The development expression and location of the ERK in the hepatic tissue and the correlation of ERK with collagen I, Ⅲ were assessed by means of immunohistochemistry. RESULTS： The expression of ERK was increased and was closely correlated with that of collagen I and Ⅲ during the development of rat fibrosis at every time point （1wk： r=0.75, 0.68, P 〈 0.05; 2 wk： r = 0.82, 0.78, P〈0.05; 3 wk： r=0.74, 0.83, P 〈 0.05）. Similarly, the expression of ERK was enhanced in human fibrotic tissues （1.068 ± 0.258 vs 0.035 ±0.011, P 〈 0.05）, which was correlated with that of collagen I and Ⅲ （r=0.87, 0.88, all P 〈 0.05）. CONCLUSION： The ERK signal pathway may play an important role in the pathogenesis of he- patic fibrosis.