卡维地洛对高血压大鼠心脏成纤维细胞胶原合成及NO含量的影响

Effect of Carvedilol on collagen synthesis and nitric oxide content of cardiac fibroblasts in spontaneously hypertensive rat

目的探讨卡维地洛对自发性高血压大鼠(SHR)心脏成纤维细胞(CFs)胶原合成及NO含量的影响及其作用机制。方法以SHR和Wistar大鼠为研究对象,采用消化法培养CFs,用硝酸还原酶法检测不同浓度(0、0.01、0.10、1.00、10.00μmol/L)卡维地洛干预下CFs培养液中的一氧化氮(NO)含量,用3H-脯氨酸掺入法观察CFs的胶原合成情况。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Wistar大鼠空白对照组(P<0.01);SHR空白对照组的3H-脯氨酸掺入率明显高于Wistar大鼠空白对照组(P<0.01)。(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3H-脯氨酸掺入率。(4)在不同浓度卡维地洛干预下,SHRCFs的3H-脯氨酸掺入率随NO含量的增高而减低,二者呈显著负相关(r=-0.943,P<0.01)。结论卡维地洛能促进CFs的NO合成,直接抑制CFs的胶原合成,进一步逆转高血压大鼠的左室重构。

Objective To explore the effects of Carvedilol on nitric oxide（NO） content in cardiac fibroblast （CFs） derived from spontaneously hypertensive rats（SHR） and Wistar rats, and to investigate the inhibiting effect on collagen synthesis of CFs in molecular level. Methods The SHR and Wistar rats were enrolled in the study. The CFs were isolated and cultured with the digestion method. Through Nitrate reductase test, the NO content was calculated at different concentration （0, 0. 01,0.10, 1.00, 10.00 μmol/L）. The course of collagen synthesis was evalualed with 3H-Proline incorporation. Results （ 1 ） After 72 hour cuhuring under basal condition, the content of NO in CFs was obviously lower in SHR control group than Wistar rats control group （ P 〈 0. 01 ）. The 3tt-Proline incorporalion in CFs was obviously higher in the SHR control group than Wistar rats control group （ P 〈 0.01 ）. （2）With the increasing of Carvedilol on CFs, the NO content significantly increased. （3）The ^3H-Proline ineorporation of CFs from SHR and Wistar rats were decreased, dependent on the concentration of Carvedilol. （4）Under intervention of different concentration Carvedilol, the ^3H-Proline ineorporation were decreased with the improving of NO contents in the CFs of SHR, and it demonstrated negatively correlation between them（ r = 0. 943, P 〈 0.01 ）. Conclusion It provided that Carvedilol induced a significant （lose dependent acceleration of NO production, inhibiting collagen synthesis, and then inversion left ventricular remodeling in hypertension rats.