【摘要】 目的:探讨缓激肽(BK)B1受体在ACEI类药物卡托普利(captopril)抑制血管紧张素Ⅱ(AngⅡ)诱导的新生大鼠心脏成纤维细胞(CFs)增殖中的作用及其可能机制。方法:经差速贴壁法培养新生大鼠CFs,随机给予AngⅡ、captopril、B2受体阻断剂icatibant和B1受体阻断剂des-Arg10,Leu9-kallidin进行干预。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后可显著升高CFsS期细胞百分率和MTT比色法测定的CFs吸光度(A490nm)值(P<0.01);Captopril10-5mol/L可明显降低AngⅡ刺激的CFsS期细胞百分率和A490nm值升高(均P<0.05),显著促进CFsNO和cGMP生成,该作用可被icatibant(10-6mol/L)部分阻断,同时阻断B1和B2受体可进一步减弱captopril的作用。结论:Captopril抑制AngⅡ诱导的CFs增殖作用部分是由BK经其B2受体介导的;同时阻断BKB1和B2受体可进一步减弱captopril抗CFs增殖效应,B1受体在B2受体阻断情况下可能起部分代偿作用,抑制CFs生长,该作用与NO、cGMP生成有关。更多还原

【Abstract】 Aim: To investigate the role and mechanism of the bradykinin（BK） B₁ receptor in the antiproliferative effects of the angiotensin-converting enzyme inhibitor （ACEI） captopril on rat cardiac fibroblasts （CFs） treated with angiotensin II （Ang II）. Methods: Neonatal rat cardiac fibroblasts were randomly treated with Ang II, captopril, B₂ receptor antagonist （icatibant） or B₁ receptor antagonist （des-Arg 10,Leu9-kallidin）. Thiazolyl blue （MTT） and flow cytometry （FCM） were used to evaluate cell number and cell cycle, respectively. Nitric oxide （NO） and intracellular cGMP level were measured by colorimetry and radioimmunoassay. Results: After incubating the fibroblasts with 10 -7 mol/L Ang II for 48 hours, the percentage of CFs in the S stage and the value of MTT A 490 nm were significantly increased （P<0.01 vs control）, and this increase was inhibited by 10 -5 mol/L captopril; however, NO and cGMP level were significantly higher than with Ang II alone （P<0.01）. 10 -5 mol/L icatibant attenuated the effects of captopril, which were blunted further by dual blockade of both B₁ and B₂. Conclusion: Acting via the B₂ receptor, BK contributes to the antiproliferative effects of ACEI on CFs. In the absence of the B₂ receptor, the B₁ receptor may assume some of the functions of the B₂ receptor and contribute to inhibition of CFs proliferation by ACEI.更多还原