叙利亚金黄地鼠胰岛局部血管紧张素Ⅱ的生成途径与机制探讨

Generative pathway and mechanism of local angiotensin Ⅱ generation in islets of Syrian golden hamsters

目的探讨以不同抑制剂阻断局部肾素血管紧张素系统(RAS)后叙利亚金黄地鼠胰岛细胞生成血管紧张素Ⅱ(AngⅡ)的变化。方法分离纯化叙利亚金黄地鼠胰岛细胞,分为对照组、卡托普利组、糜蛋白酶抑素组、抑肽酶组、α-抗胰蛋白酶组、卡托普利+糜蛋白酶抑素组共6个组,加入血管紧张素Ⅰ后按组别依次加入PBS、卡托普利(终浓度1mmol/L)、糜蛋白酶抑素(终浓度1mmol/L)、抑肽酶(终浓度1mmol/L)、α-抗胰蛋白酶(终浓度50μg/ml)、卡托普利联合糜蛋白酶抑素(终浓度均为1mmol/L)干预胰岛细胞,然后以酶联免疫分析法(ELISA)检测各组上清中AngⅡ的含量。结果卡托普利组、糜蛋白酶抑素组上清AngⅡ含量差异无统计学意义(P=0.72),但分别较不加抑制剂的对照组减少了42.50%和50.94%(P<0.01),而α-抗胰蛋白酶和抑肽酶组分别较对照组减少了20.04%和18.67%(P<0.05),卡托普利+糜蛋白酶抑素组则较对照组减少了81.82%(P<0.01)。结论胰岛局部AngⅡ的生成除经典的血管紧张素转换酶(ACE)途径之外还存在糜蛋白酶途径;非疾病状态下由ACE途径和糜蛋白酶途径所生成的AngⅡ的量无显著差异。

Objective To explore the changes in angiotensin Ⅱ （AngⅡ） produced by Langerhan islets of Syrian hamsters after blockage of reniwangiotensin system （RAS） by different inhibitors. Methods Islet cells from Syrian golden hamster were isolated and purified, and angiotensin Ⅰ was added. The experiment was then divided into six groups： control group （PBS was added）, captopril group, chymostatin group, aprotinin group, mantitrypsin group, and captoprilq-chyrnostatin group （according to inhihitors added）. The content of AngⅡ in supematant was detected by enzymeqinked immunosorbent ashy （EIdSA）. Results Compared with control group, the AngⅡ content decreased by 42. 50% and 50. 94% in eaptopril group and chymostatin group, respectively （P〈0. 01 ）, while no significant difference existed between the two groups （P=0. 72） ; the AngⅡ content in mantitrypsin group and aprotinin group decreased by 20. 04% and 18. 67 % compared with that in control group （P〈0.05）; the AngⅡ content decreased by 81.82 % in captopril＋chymostatin group compared with that in control group （P〈0.01）. Conclusions Besides the typical pathway of islets local AngⅡ generation of angiotensinconverting enzyme （ACE）, there exists the chymase pathway. In the disease-free condition, no significant difference was found between the AngⅡ generated by ACE way or chymase way.