贝那普利对肝纤维化大鼠胰岛样生长因子结合蛋白-2表达的影响

Effect of benazepril on insulin-like growth factor binding protein-2 expression in hepatic fibrosis rats

目的研究血管紧张素转换酶抑制剂(angiotensin converting enzyme inhibitor,ACEI)贝那普利对大鼠肝纤维化的疗效以及对肝纤维化大鼠胰岛素样生长因子结合蛋白-2(insulin-like growth factor binding protein-2,IGFBP-2)表达的影响。方法22只健康雄性Wistar大鼠随机分为3组:正常对照组(n=6),模型组(n=8),贝那普利预防治疗组(n=8)。除正常对照组外,模型组和贝那普利预防治疗组均给予大鼠首次皮下注射40%CCl4油剂5 ml/kg,以后每次皮下注射40%CCl4 2 ml/kg,每周两次。给予正常对照组相同剂量的油剂皮下注射。同时贝那普利预防治疗组从实验第1天开始给予贝那普利10 mg/(kg.d)灌胃,直至实验结束。于8周末,分别杀死大鼠,留取血及肝组织标本备用。肝组织进行常规HE及Masson三色染色,酶联免疫法测定血清IGFBP-2,免疫组织化学染色肝组织IGFBP-2。结果贝那普利有明显抗大鼠肝纤维化的疗效,模型组IG-FBP-2在血清和肝组织的表达增加(P<0.05),贝那普利预防治疗组比模型组血清和肝组织IGFBP-2的表达减少(P<0.05)。结论贝那普利抗肝纤维化的机制可能与其降低血清及肝组织IGFBP-2的表达有关。

Objective To explore the protective effects of angiotensin converting enzyme inhibitor（ACEI） benazepril on insulin-like growth factor binding protein-2（IGFBP-2） expression in rats of hepatic fibrosis induced by carbon tetrachloride（CCl4）.Methods Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride（CCl4） in rats.Twenty-two Wistar male rats were randomly divided into normal control group（n=6）,model group（n=8）,benazepril treatment group（n=8）.The rats in model group and benazepril treatment group were firstly given the intraperitoneal injection of 40% CCl4 5 ml/kg,and followed by intraperitoneal injection of 40% CCl4 2 ml/kg twice a week.The rats in control group were given intraperitoneal injection of the same dosage of oil.From the first day of intraperitoneal injection to the end of experiment,the rats in benazepril treatment group were given benazepril 10 mg/（kg · d）by gastric gavage.At the end of week 8,blood samples and liver tissues were collected.Histopathological changes of liver tissue were observed with hematoxylin-eosin（HE） and Masson trichrome staining.Serum IGFBP-2 levels were examined by enzyme-linked immunosorbent assay（ELISA）.IGFBP-2 expression in liver was evaluated by immunohistochemistry.Results The expression of IGFBP-2 in serum and liver tissues were significantly higher in model group than in normal control group（P0.05）.Compared wtih model group,expression of IGFBP-2 in serum and liver tissues significantly decreased in benazepril treatment group（P0.05）.Benazepril attenuated the degree of hepatic fibrosis.Conclusion Benazepril can delay the degree of hepatic fibrosis by decreasing the expression IGFBP-2.