肝细胞生长因子和C-met在肝纤维化肝部分切除后残余肝组织中的表达

Expression of hepatic growth factor and C-met in reserved liver tissue after partial hepatectomy of hepatic fibrosis

目的探讨肝细胞生长因子(HGF)和C-met在纤维化肝部分切除后残余肝组织中的表达变化。方法雄性SD大鼠130只,随机分为正常组(n=7)、正常肝部分切除组(n=50)、肝纤维化组(n=7)和纤维化肝部分切除组(n=66)。正常肝部分切除组和纤维化肝部分切除组分别在术后12h、1d、3d、5d、7d和14d取材,运用免疫组织化学和Western blotting方法,检测残肝组织中HGF、C-met的表达。结果免疫组织化学显示,正常肝部分切除组,HGF表达于术后12h达高峰,并维持高峰平台,7d后逐渐降低,于14d接近术前水平;C-met术后迅速上升,3d达到高峰,而后逐步下降,14d降回术前水平。纤维化肝部分切除组,HGF表达于术后迅速下降,12h又迅速上升,于1d时达高峰,然后逐步下降,14d降至最低点;C-met术后迅速下降,12h开始缓慢下降,于术后3d达最低点,后缓慢上升,7d又迅速上升,14d达最高点。Western blotting显示,HGF、C-met蛋白条带变化规律与免疫组织化学结果吻合。结论HGF和C-met同时高水平表达有利于肝细胞的分裂增殖,提示HGF和C-met表达不同步,可能是纤维化肝术后再生困难的重要原因。

Objective To study the expression of hepatic growth factor（HGF） and C-met in reserved liver tissue after partial hepateetomy of rats with hepatic fibrosis. Methods Totally 130 SD rats were randomly divided into four groups： normal group （n = 7 ） , group of normal rats with partial hepatectomy（ n = 50） , hepatic fibrotic group（ n = 7 ） , and group of hepatic fibrotie rats with partial hepatectomy（ n = 66）. Rats were killed after operation 12 hours, 1 day, 3 days, 5 days, 7 days and 14 days separately, then HGF and C-met of reserved liver tissues were detected with immunohistochemistry staining and Western blotting. Results In the group of normal rats with partial hepatectomy, immunohistochemistry staining indicated that the expression of HGF and C-met increased to get the peak point after partialhepatectomy 12 hours and 3 days respectively, and HGF maintained at the high level to the 7th day, then decreased gradually, finaly approched to the level of pro-operation at 14th day, but C-met fell sharply,and declined to the the level of pro-operation at the 14th day. In the group of hepatic fibrotic rats with partial hepatectomy, the expression of HGF and C- met decreased sharply after operation 12 hours, next HGF increased to get the peak point at the 1 st day, and then declined speedily, and decreased to the bottom at the 14th day, but C-met declined to the bottom at the 3rd day, then increased slightly till the 7th day, affter that increased sharply to the summit at the 14th day. Western blotting analysis showed the results of HGF and C-met coincided with that of immunohistochemistry. Conclusion The high isochronous expression of HGF and C-met in hepatic tissue is propitious to hepatocellular division, Which indicates that the expresson out of step of HGF and C-met might be the key reason of hard regeneration of fibrosis liver after operation.