缓激肽对卡托普利抑制新生大鼠心脏成纤维细胞增殖作用的影响

来源 :临床心血管病杂志 | 被引量 : 0次 | 上传用户:jydliu
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目的:探讨卡托普利在血管紧张素Ⅱ(AngⅡ)诱导的新生大鼠心脏成纤维细胞(CFs)增殖中的作用和缓激肽(BK)对该作用的影响及机制。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(A组),卡托普利组(B组),AngⅡ组(C组),AngⅡ加卡托普利组(D组),HOE-140组(E组)和AngⅡ加卡托普利加HOE140组(F组)。采用四氮唑盐(MTT)比色法测细胞数,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A组比较,C组孵育细胞48后可显著增加CFs S期细胞百分率和MTT比色法测定的CFs吸收度(A)(分别P< 0.01.P<0.05);B组明显降低Ang Ⅱ作用下的CFs S期细胞百分率和A值,而NO含量和细胞内cGMP水平均显著高于C组(均P<0.05);E组可部分阻滞卡托普利的作用,F组的CFs S期细胞百分率和A值均明显高于D组(分别P<0.01,P<0.05),NO含量和细胞内cGMP水平均显著低于后者(均P<0.05)。结论:卡托普利可能通过NO、cGMP途径抑制Ang Ⅱ诱导的CFs增殖,而BK经β3受体部分介导卡托普利的抗增殖肥厚作用。 AIM: To investigate the effect of captopril on the proliferation of neonatal rat cardiac fibroblasts (CFs) induced by angiotensin Ⅱ (Ang Ⅱ) and the effect and mechanism of bradykinin (Bk) on this effect. Methods: CFs of neonatal rats cultured by differential adherence method were randomly divided into 6 groups: blank control group (group A), captopril group (group B), Ang Ⅱ group (group C) (Group D), HOE-140 group (group E) and AngⅡ-captopril HOE140 group (group F). Cell number was measured by MTT colorimetric assay, cell cycle was detected by flow cytometry (FCM), nitric acid reductase and radioimmunoassay were used to determine the content of NO in the cultured CFs supernatant and intracellular cGMP level. Results: Compared with group A, group C could significantly increase the percentages of cells in CFs S phase and CFs absorbance (A) (P <0.01, P <0.05, respectively) Ⅱ, while the content of NO and the level of intracellular cGMP were significantly higher than those in group C (all P <0.05); the effect of captopril was partially blocked in group E, and the effect of captopril in group F The percentage of cells in C phase and the value of A in CFs were significantly higher than those in group D (P <0.01, P <0.05, respectively). The levels of NO and intracellular cGMP in CFs were significantly lower than those in group D (all P <0.05). Conclusion: Captopril may inhibit the proliferation of CFs induced by Ang Ⅱ through NO and cGMP, while BK partly mediates the antiproliferative effect of captopril through β3 receptor.
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