福辛普利对大鼠肝纤维化的影响

Effects of fosinopril on liver fibrosis in rats

目的研究血管紧张素转换酶抑制剂福辛普利抗大鼠肝纤维化的作用。方法雄性清洁级SD大鼠40只,随机分成5组:阴性对照组(n=5),腹腔注射植物油,每日单蒸水灌胃;模型组(n=5),腹腔注射CCl4,每日单蒸水灌胃;阳性对照组(n=10),造模方法同模型组,每日用秋水仙碱0.2mg/kg灌胃;福辛普利小剂量组(n=10),造模同时每日用福辛普利0.1mg/kg灌胃;福辛普利大剂量组(n=10),造模同时每日用福辛普利0.2mg/kg灌胃。于8周末处死大鼠,测定血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平,放射免疫法检测透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原肽(PCⅢ)和Ⅳ型胶原(C-Ⅳ)含量;取肝组织行HE染色及病理分级;于给药前、第4周和第8周测量大鼠收缩压及心率。结果与模型组比较,病理检查显示应用福辛普利后大鼠肝纤维化程度明显减轻(P<0.05),肝细胞损害亦较轻,且反映肝纤维化的指标HA、LN、PCⅢ和C-Ⅳ均显著降低(P<0.01);与给药前比较,福辛普利组给药后血压明显下降,且大剂量组血压下降更明显(P<0.05)。结论福辛普利有明显抑制大鼠肝纤维化形成的作用。

Objective To investigate the effects of angiotensin convertase inhibitor fosinopril on preventing hepatic fibrosis of rats.Methods The rat hepatic fibrosis model was reproduced by intraperitoneal injection of CCl4 for 8 weeks.All rats were randomly divided into five groups：normal group（N,n=5） with intraperitoneal injection of peanut oil,3ml/kg,twice per week,for 8 weeks;model group（M,n=5） received intraperitoneal injection of 50% CCl4 vegetable oil mixture,3ml/kg,twice per week,for 8 weeks;positive control group（P,n=10）,in which rats received colchicine by intragastric administration;low dose of fosinopril group（FL,n=10）,in which rats were administered daily with 0.1mg/kg of fosinopril;and high dose of fosinopril group（FH,n=10）,in which rats were administered daily with 0.2mg/kg of fosinopril.At the end of the 8th week all rats were sacrificed with anesthesia.Whole blood was centrifuged and the supernatant was stored at-20℃.The liver tissue was harvested at the similar anatomica region,fixed with 10% neutral formalin,paraffin embedded,and then sectioned.The serum biochemical parameters,fibrosis markers and the pathological grading of hepatic fibrosis were then determined.Results The digree of hepatic fibrosis in animals of FL and FH group was significantly lower,and the serum contents of HA,LN,PCIII,C-IV,AST and ALT were also reduced obviously compared with those in model group（P〈0.01 or P〈0.05）.The blood pressure of animals in both FH and FL groups declined obviously after administration of fosinopril compared with that before the treatment,and more obvious decline was found in FH group than in FL group.Conclusion Fosinopril can obviously inhibit the hepatic fibrosis induced by CCl4 in rats.