卡维地洛对自发性高血压大鼠心脏成纤维细胞增殖的影响

Effect of Carvedilol on Proliferation of Cardiac Fibroblasts in Spontaneously Hypertensive Rats

【目的】研究卡维地洛对自发性高血压大鼠(SHR)和实验性大鼠(Wistar)心脏成纤维细胞(CFs)一氧化氮(NO)含量的影响,探讨卡维地洛抑制CFs增殖的作用机制。【方法】以12周龄SHR10只为对象,培养CFs,分为空白对照组和卡维地洛干预组;另以Wistar健康大鼠10只的CFs为正常对照组。采用消化法培养CFs,用硝酸还原酶法检测不同浓度卡维地洛干预下CFs培养液中的NO含量,用改良的MTT比色法观察CFs的增殖状况。【结果】①在基础状态下培养72h,SHR空白对照组的NO含量明显低于正常大鼠空白对照组(P<0.01);SHR空白对照组的OD值明显高于正常大鼠空白对照组(P<0.05)。②卡维地洛以浓度依赖的方式促进CFs的NO含量增加。③卡维地洛以浓度依赖的方式抑制CFs的OD值。④在不同浓度卡维地洛干预下,SHRCFs的OD值随NO含量的增高而减低,二者呈显著负相关(r=-0.949,P<0.01)。【结论】卡维地洛能促进CFs的NO合成,直接影响了CFs的增殖,进一步抑制高血压的左室重构。

[Objective] To observe the effect of carvedilol on nitric oxide（NO） synthesis in cardiac fibroblast （CFs） derived from spontaneously hypertensive rats（SHR） and Wistar rats,and to investigate the antiproliferation of CFs in molecular level. [Methods]Ten 12-week old SHR were used in this study, and the cultured CFs were divided into blank control group and carvedilol intervention group. The CFs derived from healthy Wistar rats were cultured as the normal control group. The CFs were isolated and cultured with the method of digestion method. Through Nitrate reductase test, the NO content were calculated. The growth of CFs was assessed by modified MTT methods. [Results] 1. After 72-hour culture under basal condition, the content of NO in CFs was obviously lower in the hypertensive blank control group than that in the Wistar rats normal blank control group （ P 〈0.01）. The MTT OD value in CFs was obviously higher in the hypertensive blank control group than that in the Wistar rats normal blank control group （ P 〈0.05）. 2.With the increase of concentration of carvedilol on CFs, the NO content significantly increased. 3.The MTT OD value of CFs from SHR and Wistar rats was decreased in a concentration-dependent manner of carvedilol.4.Under carvedilol intervention with different concentrations, the MTT OD values of were decreased with the enhancement of the NO contents in the CFs of SHR, and there was a significantly negative correlation between them（r=- 0. 949, P 〈0.01）. [Conclusion]Carvedilol could induce a significant dose-dependent acceleration of NO production. NO could inhibit CFs proliferation, and then inhibit the left ventricular remodeling of hypertension.