大鼠肝纤维化进程中血管紧张素转化酶2-血管紧张素（1-7）-Mas受体的动态变化情况

Differential expression in ACE2, Ang（l-7） and Mas receptor during progression of liver fibrosis in a rat model

目的探讨大鼠肝纤维化形成过程中血管紧张素转化酶2-血管紧张素（1-7）-Mas[ACE2-Ang（1-7）-Mas]受体轴各组分的变化情况。方法成年雄性Wistar大鼠36只，随机取6只为正常对照组，余30只用于制备cc4诱导大鼠肝纤维化模型，分别在造模第15、30、45、60、75天随机处死6只；取各组大鼠肝组织进行HE及Masson染色观察其病理学改变情况，酶联免疫吸附试验检测肝组织Ang（1—7）的水平，免疫组织化学方法检测肝组织ACE2、Mas受体的表达情况，Real-timePCR检测肝组织ACE2、Mas受体mRNA的表达隋况。对多组间数据进行单因素方差分析，进而的两两比较采用LSD-t检验法或者Dunnet-T3检验法。结果病理学结果显示，正常组大鼠肝细胞规整，肝小叶结构正常；模型组肝细胞排列紊乱，部分细胞胞质疏松、脂肪变性，呈空泡状，汇管区有胶原沉积，肝小叶结构紊乱，随着造模时间的延长肝小叶内逐渐形成纤维间隔。与正常对照组比较，15、30、45、60、75d各时间点模型组Ang0-7）含量均增高（67．79土9．35、92．86±10．40、110．47土14．40、142．89士16．16、132．13士12．9l与50．23士11．41，F=49．05，P〈0．01），并呈逐渐上升趋势，15、30、45、60d模型组相邻两组间比较，差异均有统计学意义∽〈0．05），但第60天至第75天增加不明显。ACE2、Mas受体的蛋白和mRNA表达水平的变化趋势与之一致。结论ACE2-Ang（1-7）-Mas受体轴各成分参与肝纤维化的发生和发展过程。

Objective To investigate the changes in expression of the ACE2/Ang（1-7）/Mas receptor axis＇ components that occur during progression of liver fibrosis using a rat model system. Methods Thirty-six adult male Wistar rats, were randomly assigned to groups of normal control （n = 6; no manipulation） and liver fibrosis （11 = 30; given a subcutaneous injection of 40% chronic carbon tetrachloride （CCI4））. At post-injection days 15, 30, 45, 60 and 75, 1 control rat and 6 modeled rats were sacrificed for analysis. Histopathological analysis of liver tissue was performed with hematoxylin-eosin and rapid Masson staining. Protein expression level of Ang（1-7） was determined by enzyme-linked immunosorbent assay, and of ACE2 and Mas receptor was evaluated by immunohistochemistry. Real-time PCR was used to measure the mRNA expression levels of ACE2 and Mas receptor. Results The expression levels of ACE2, Ang（1-7） and Mas receptor showed a statistically significant upward trend that followed the progression of fibrosis up to post-injection day 60 （P 〈 0.01）, but thesignificant increase was not seen from day 60 to day 75. Conclusion Each component of the ACE2/Ang（1-7）/ Mas receptor axis shows differential expression during the development of liver fibrosis and may contribute to disease progression.