缓激肽β_2受体介导卡托普利抑制心脏成纤维细胞的增殖作用  

Bradykinin β_2 Receptor Partially Mediates the Antiproliferative Effects of Captopril on Cardiac Fibroblasts in Neonatal Rats

作　　者：冯丹[1] 徐江[1] 邹军[2] 

机构地区：[1]武汉大学医学院生理系 [2]武汉大学中南医院老年病研究所,湖北武汉430071

出　　处：《高血压杂志》2005年第4期235-239,共5页Chinese Journal of Hypertension

摘　　要：目的探讨卡托普利(Captopril)在血管紧张素Ⅱ(AngⅡ)诱导的新生大鼠心脏成纤维细胞(CFs)增殖中的作用及缓激肽(BK)β2受体对此作用的影响及机制。方法经差速贴壁法培养的新生大鼠CFs,随机分为6组:空白对照组,卡托普利组,AngⅡ组,AngⅡ+卡托普利组,Hoe140组和AngⅡ+卡托普利+Hoe140组。采用四氮唑盐(MTT)比色法测细胞数目,流式细胞仪技术(FCM)检测细胞周期,硝酸还原酶法和放射免疫分析技术分别测定培养CFs细胞上清液中NO含量和细胞内cGMP水平。结果与空白对照组比较,AngⅡ10-7mol/L孵育细胞48h后可显著增加CFsS期细胞百分率和MTT比色法测定的CFs吸光度(A490nm)值(分别P<0.01,P<0.05);ACEI类药物卡托普利10-5mol/L可明显降低AngⅡ作用下的CFsS期细胞百分率和A490nm值,而NO含量和细胞内cGMP水平均显著高于AngⅡ组(均P<0.05);缓激肽β2受体阻断剂Hoe14010-6mol/L可部分阻断卡托普利的作用。结论缓激肽β2受体部分介导了卡托普利抑制AngⅡ诱导的CFs增殖作用,BK该作用与NO、cGMP生成有关。Objective To investigate the role of bradykinin(BK) β2 receptor in the inhibitory effect of Captopril on proliferation of cardiac fibroblasts(CFs) induced by angiotensin Ⅱ(Ang Ⅱ). Methods Neonatal rat cardiac fibroblasts were randomly divided into 6 groups: control, Captopril, Ang Ⅱ, Ang Ⅱ+Captopril, Hoe-140, and Ang Ⅱ+Captopril+Hoe-140. Thiazolyl blue(MTT) and flowcytometry (FCM) were used to evaluate cell number and cell cycle. Nitric oxide (NO) and intracellular cGMP were measured by colorimetry and radioimmunoassay. Results After incubating the fibroblasts with 10~ -7 mol/L Ang Ⅱ for 48 hours, the value of MTT A 490 nm and the percentage of CFs in the S stage were significantly increased (P<0.05 and P<0.01 vs control, respectively), which was inhibited by 10~ -5mol/L Captopril. However, Captopril significantly increased supernant NO and intracellular cGMP (P< 0.05 for both). 10~ -5 mol/L Hoe-140 (a specific bradykinin β2receptor antagonist) partially blocked the inhibitory effects of Captopril. Conclusion ACE inhibitors inhibites the proliferation of CFs induced by Ang Ⅱ which may be partially mediated by bradykinin β2receptor. NO and cGMP may involve in the effect of BK.=

关 键 词：心脏成纤维细胞 卡托普利 增殖作用 受体介导 血管紧张素Ⅱ(AngⅡ) mol/L 缓激肽(BK) 流式细胞仪技术 ACEI类药物 免疫分析技术 硝酸还原酶法 抑制AngⅡ 新生大鼠 NO含量 S期细胞 cGMP CFs 比色法测定 受体阻断剂 β2受体 

分 类 号：R541[医药卫生—心血管疾病]