肝细胞生长因子激活抑制因子在肝硬化大鼠部分肝切除后肝再生过程中的表达

HGFA and its inhibitors manifested differential expressions during liver regeneration after partial Hepatectomy in cirrhotic rat model

目的 研究肝细胞生长因子激活因子（HGFA）的抑制因子（HAI-1、HAI-2）在硬化和正常肝脏再生中的表达,探讨HAI-1、HAI-2的生物学效应及其与肝再生的关系.方法 采用40％四氯化碳油溶液背部皮下注射法建立大鼠肝硬化模型.实验组实施70％肝脏切除术,建立部分肝切除术后再生模型,以健康大鼠作为对照.分别于术前及术后3、6、12、24、48 h处死大鼠并留取标本检测.使用实时PCR技术检测脾原性HAI-1 mRNA、HAI-2 mRNA表达情况.结果 肝硬化大鼠各时间点血清HGFA浓度均显著低于对照组（P＜0.05）,肝硬化大鼠HAI-1 mRNA表达量持续高于对照组（P＜0.05）,而两组大鼠之间HAI-2 mRNA表达量差异无统计学意义（P＞0.05）.结论 肝硬化大鼠部分肝切除术后再生过程中HGFA的合成分泌较健康大鼠低,这可能导致了肝细胞生长因子（HGF）前体活化不足,以致再生速率缓慢.HAI-2并没有参与肝脏的损伤修复进程.

Objective To investigate the differential expression of hepatocyte growth factor activator （HGFA） and its inhibitors （HAI-1,HAI-2） during cirrhotic and normal liver regeneration after partial hepatectomy,and to explore the causes of the delayed liver regeneration after partial hepatectomy in cirrhotic rat model.Methods We used 40% CCl4 subcutaneous injection to establish the cirrhotic rat model,and then performed 70% liver resection for the experimental group together with no operation for the healthy rats as control group.Rats in each group after 3 hours,6 hours,12 hours,24 hours and 48 hours were randomly sacrificed and specimens were collected.The serum HGFA was detected by enzyme-linked immunosorbent assay （ELISA）,and we used RT-PCR to detect the mRNA expressions of HAI-1 and HAI-2 in splenic tissue.Results The serum HGFA level in cirrhotic rats at each time point was all significantly lower than that in the control group （P 〈0.05）.The expression of HAI-1 mRNA in cirrhotic rats was sustained at a higher level than that in the control group （P 〈 0.05）,but there was no significant difference on the HAI-2 mRNA expression between the two groups （P 〉 0.05）.Conclusions The synthesis of HGFA during the liver regeneration after partial hepatectomy in cirrhosis rats is lower compared with healthy rats,which may lead to the insufficient activation of HGF precursor,eventually causing the slow liver regeneration.HAI-2 may not be involved in the healing process of liver.