FGFR3在大鼠肝硬化模型中的动态表达研究

The experimental investigation into the expression of fibroblast 3 growth factor receptor in the hepatic tissues during the development of hepatic cirrhosis in rats

目的:观察大鼠肝硬化形成过程中成纤维细胞生长因子受体3(Fibroblast growth factor receptor 3,FGFR3)的表达变化。方法:70只雄性SD大鼠,随机取10只作为对照组,其余60只作为肝硬化组。采用剂量频次渐变式四氯化碳(CCl4)腹腔内注射建立肝硬化大鼠模型。检测2组大鼠的血清ALT、体重、肝体比,病理组织行包括HE和嗜银染色,并采用荧光定量聚合酶链反应(real-time PCR)和蛋白质印迹(Western blot)检测FGFR3基因和相应蛋白在肝硬化形成过程中的表达变化。结果:肝硬化组大鼠的血清ALT、肝体比和死亡率均显著高于对照组(P均<0.01);而体重则显著低于对照组(P<0.01);肝硬化组大鼠肝组织大体观察、HE染色及嗜银染色均呈明显肝硬化表现,而对照组则无该表现;real-time PCR及Western-blot结果显示,FGFR3在肝硬化形成过程中总体表达逐渐增强。结论:剂量频次渐变式CCl4腹腔内注射法是一种高效、低成本的大鼠肝硬化建模方法。而肝组织FGFR3在肝硬化发生、发展过程中的动态表达在一定程度上反映了肝纤维化及肝硬化程度。

Objective To monitor the expression of Fibroblast growth factor receptor 3 （FGFR3） in hepatic tissues during the development of hepatic cirrhosis in rats. Methods Seventy male SD rats were randomly divided into two groups. Ten rats served as the control group and other rats were employed as the liver cirrhosis models. The models of hepatic cirrhosis was established by gradually increasing the frequency and dosage of intraperitoneal injection of carbon tetrachloride （CCl4）. The body weight, ratio between liver weight and body weight and serum ALT were measured. Hepatic pathological status by HE staining and argyrophil granules staining were observed. The expression of FGFR3 gene and protein in hepatic cirrhotic tissues were detected by real-time PCR and Western blot during the development of cirrhosis. Results The serum ALT level in the group with hepatic cirrhosis was significantly higher than that of the control group （P〈0.01）. The ratio between liver weight and body weight in the group with hepatic cirrhosis was significantly lower than that of the control group （P〈0.01）. The survival rate in the group with hepatic cirrhosis was also lower significantly than that of the control group （P〈0.01）. Pathological manifestation of hepatic cirrhosis was observed in the experimental group. The expression of FGFR3 gene and protein increased gradually during the development of hepatic cirrhosis. Conclusions The method of gradually increasing the frequency and dosage of intraperitoneal injection of carbon tetraehloride was effective and of low-cost for establishing the model of hepatic cirrhosis in rats. The dynamic expression of FGFR3 could reflect the degree of hepatic fibrosis or cirrhosis.