依那普利对肝纤维化大鼠门静脉血流动力学及基质金属蛋白酶1组织抑制剂表达的影响  

The effect of enalapril on hemodynamics of portal venous and expression of tissue inhibitor of metallo-proteinases-1 in rats of cirrhosis

作　　者：魏常胜[1] 王宇[2] 张忠涛[2] 周延忠[2] 马雪梅[2] 

机构地区：[1]首都医科大学附属北京安贞医院普外科,100029 [2]首都医科大学附属北京友谊医院普外科

出　　处：《中国医药》2010年第11期998-1000,共3页China Medicine

摘　　要：目的 探讨血管紧张素转换酶抑制剂（ACEI）依那普利对肝纤维化大鼠门静脉血流动力学和基质金属蛋白酶1组织抑制剂（TIMP-1）表达的影响. 方法 30只大鼠完全随机分为正常对照组、模型组、治疗组,每组10只.模型组和治疗组通过四氯化碳（CCl4）损伤制备肝纤维化门静脉高压模型,治疗组在造模的同时用依那普利灌胃.3组大鼠均测量门静脉压（PVP）、平均动脉压（MAP）、门静脉血流速度（BFR）;进行肝纤维化分级和胶原沉积半定量检测;检测TIMP-1的蛋白及mRNA表达并进行半定量分析. 结果 模型组的PVP高于正常对照组和治疗组,治疗组亦高于正常对照组均（P＜0.05）;模型组和治疗组的MAP均低于正常对照组（均P＜0.05）;模型组的BFR明显低于正常对照组和治疗组（均P＜0.05）.模型组肝纤维化V级的大鼠明显多于治疗组（P＜0.05）,模型组和治疗组肝细胞变性/坏死（＋）及（＋＋）的大鼠明显多于正常对照组（P＜0.01）,模型组和治疗组炎性细胞浸润（＋）及（＋＋）的大鼠明显多于正常对照组（P＜0.01或P＜0.05）.治疗组和模型组的胶原沉积面积[（6.393±2.113）×10-2、（10.030±3.565）×10-2]均明显大于正常对照组[（1.538±0.458）×10-2,均P＜0.01],但治疗组明显小于模型组（P＜0.01）.治疗组与模型组比较TIMP-1的蛋白表达有明显下降,TIMP-1 mRNA的表达亦有明显下降,但模型组和治疗组两指标明显高于正常对照组（均P＜0.05）. 结论 依那普利可以有效地改善肝纤维化大鼠的门静脉血流动力学;亦可有效地下调CCl4引起的肝纤维化大鼠TIMP-1的蛋白和mRNA表达,进而抑制大鼠肝纤维化的发展.Objective To investigate the effect of Enalapril on hemodynamics of portal venous and the expression of tissue inhibitor of metallo-proteinases-1（TIMP-1）. Methods Hepatic cirrhosis with portal hypertension was induced in 30 S-D rats by CC14 treatment.These rats were randomly assigned to one of the following groups：normal control,model group and enalapril treatment group.Rats of enalapril treatment group were then treated respectively with enalapril（intragastric administration）,concurrently with CCl4.And then the rats were anaesthetized and the portal venous pressure（PVP）,mean arterial blood pressure（MAP）and portal venous blood flow rate （BFR）was measured.Formalin-fixed sections were stained with H＆E and Masson.Deposit of collagen and fibrosis of the liver was assessed histologically.And then the expressions of TIMP-1 were measured by immunohistochemistry.Relative mRNA expressions of TIMP-1 were determined by semi quantitative reverse transcriptase-polymerase chain reaction（RT-PCR）. Results The PVP was significantly increased in the model group than that in the normal control and enalapril treatment group（P 〈0.05）.The MAP was significantly decreased in the model group and enalapril treatment group than that in the normal control Portal venous blood flow rate was also obviously lower in the model group than that in other groups（P 〈 0.05）.Enalapril treatment group had significantly reduced stages of fibrosis and collagen semi quantitative of Masson stain than the model group（P 〈0.05）.The extent of hepatic cell degeneration and necrosis were significantly increased in the model group and enalapril treatment group than that in the normal control（P 〈0.01）.The same results were found in liver cells of inflammatory infiltration.The expression of protein and mRNA of TIMP-1 were significantly up-regulated in the model group than that in other groups（P 〈0.05）. Conclusions Enalapril can effectively improve hepatic hemodynamics and lower the PVP in cirrhosis.Enalapril

关 键 词：肝硬化 金属蛋白酶1组织抑制剂 血液动力学现象 

分 类 号：R575.2[医药卫生—消化系统]