肝细胞生长因子与肝再生增强因子融合基因对大鼠肝纤维化的影响

目的研究肝细胞生长因子（HGF）与肝再生增强因子（ALR）融合基因对大鼠实验性肝纤维化的治疗作用，并探讨其可能作用机制。方法采用80只SD大鼠建立肝纤维化模型，将成模大鼠随机分为模型组、单纯HGF组、单纯ALR组和HGF／ALR融合基因组，并取10只同批次大鼠作正常组，分别检测各组血清透明质酸（HA）、层粘蛋白（LN）、Ⅲ型前胶原（PCⅢ）和Ⅳ型胶原（CIV）水平，同时留取肝组织标本用于病理学观察和增殖细胞核抗原（PCNA）、原癌基因（c-jun）测定。结果各治疗组大鼠肝纤维化和肝细胞再生程度均较模型组改善，但以HGF／ALR组尤为明显。HGF／ALR组血清HA、LN、PCⅢ和CⅣ水平均较单纯HGF组和ALR组显著下降（均P〈001），PCNA表达水平较单纯HGF组和ALR组显著增强（P〈0．01），而c-jun表达水平则较单纯HGF组和ALR组减弱（P〈001）。结论HGF与ALR的融合基因具有较好改善大鼠实验性肝纤维化的作用，并可能通过促进肝细胞增殖和抑制c-jun的表达，从而发挥其抗肝纤维化作用。

Fusion gene of hepatocyte growth factor and augmenter of liver regeneration inhibits hepatic fibrosis in rats

Objective To evaluate the therapeutic effects of fusion gene of hepatocyte growth factor （HGF） and augmenter of liver regeneration （ALR） on hepatic fibrosis in rats. Methods Eighty SD rats with induced hepatic fibrosis,were randomly divided into 4 goups： model group,HGF group,ALR group and HGF/ALR group, and 10 normal SD rats were used as controls. Serum levels of hyaluronic acid （HA）,laminin （LN）,precollagen III （PC III ） and collogenIV （CIV） were measured after treatment. Liver tissues were collected for detecting proliferating cell nuclear antigen （PCNA） and c-jun. Results In HGF,ALR and HGF/ALR groups,different degree of amilioration in hepatic fibrosis and hepatocyte regeneration was obtained, compared with model group,and that was most marked in HGF/ALR group. Compared with HGF and ALR groups,serum levels of HA, LN, PC Ⅲ and CⅣ was significantly declined in HGF/ALR group （P〈0.01）,and the expression of PCNA was increased,while the expression of c-jun was decreased （P〈0.01）. Conclusion The fusion gene of HGF and ALR can effectively inhibit hepatic fibrosis in rats by increasing the expression of PCNA and decreasing the expression of c-jun.