缓激肽B_1受体在卡托普利抑制心脏成纤维细胞增殖中的作用  

BRADYKININ B_1 RECEPTOR ANTAGONIST REDUCES THE ANTIPROLIFERATIVE EFFECTS OF CAPTOPRIL ON CARDIAC FIBROBLASTS IN NEONATAL RATS

作　　者：邹军[1] 王虹[1] 冯丹[2] 徐江[2] 

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

出　　处：《中国应用生理学杂志》2006年第4期469-473,共5页Chinese Journal of Applied Physiology

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。To investigate the role and mechanism of the bradykinin（BK） B1 receptor in the antiproliferative effects of the angiotensinconverting enzyrne 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, 132 receptor antagonist （icatibant） or B1 receptor antagonist （des-Arg^10, Leu^9-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 A490 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 Ⅱalone （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.

关 键 词：缓激肽B1受体 缓激肽B2受体 卡托普利 血管紧张素Ⅱ 心脏成纤维细胞 

分 类 号：Q463[生物学—生理学]