阿伐他汀对内皮素-1 诱导的新生大鼠心肌成纤维细胞增殖和胶原合成的影响

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (9): 1058-1061.

阿伐他汀对内皮素-1 诱导的新生大鼠心肌成纤维细胞增殖和胶原合成的影响

王艾丽¹, 陈玲玲², 胡剑峰¹, 程新耀¹

¹武汉大学中南医院超声心动图室, 武汉430071, 湖北;
²麻城市妇幼保健院儿科, 麻城438300, 湖北

收稿日期:2007-07-18 修回日期:2007-09-14 出版日期:2007-09-26 发布日期:2020-10-30
作者简介:王艾丽, 女, 硕士, 主管技师, 研究方向:冠心病基础与临床。Tel:027-63633670 E-mail:wangal07@126.com

Effects of atorvastatin on the proliferation and collagen synthesis of cardiac fibroblasts induced by endothelin-1

WANG Ai-li¹, CHENG Ling-ling², HU Jian-feng¹, CHENG Xin-yao¹

¹Department of Ultrasoundcardiogram, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China;
²Department of Pediatrics, Macheng Maternity and Children's Hospital, Macheng 438300, Hubei, China

Received:2007-07-18 Revised:2007-09-14 Online:2007-09-26 Published:2020-10-30

摘要/Abstract

摘要： 目的:观察阿伐他汀对内皮素-1(endothelin-1ET-1) 诱导的心脏成纤维细胞(cardiac fibroblast, CFs)增殖和胶原合成的影响及可能机制。方法:经差速贴壁法培养新生大鼠CFs, 随机分为4 组:空白对照组, ET-1(10^-6 mol/L) 组, 阿伐他汀(1.0×10^-4 mol/L)组, ET-1+阿伐他汀(10^-7～10^-4mol/L) 组。采用四氮唑盐(MTT) 比色法测定细胞数目, 流式细胞仪(FCM) 检测细胞周期, 液体闪烁计数仪测定[³H]-脯氨酸掺入率, 硝酸还原酶法测定上清液中NO 含量。结果:与空白对照组比较, ET-1(10^-6 mol/L) 孵育细胞48 h 后可显著增加MTT 比色法测定的CFs 吸光度A490值和[³H]-Pro 掺入率, 降低CFs 生成NO 的量(P<0.01);随着阿伐他汀浓度的增高, CFs 的A490值和[³H]-Pro 掺入率呈明显的递减趋势(P<0.01), 促进CFs NO 的生成(P<0.01);细胞周期分析表明, 与空白对照组比较ET-1 能显著提高S 期细胞百分率(P<0.01), 1.0×10^-4 mol/L 阿伐他汀抑制ET-1 诱导S 期细胞百分率上升(P<0.01)。结论:阿伐他汀呈浓度依赖性抑制ET-1 诱导的CFs 增殖和胶原合成, 该作用可能与NO 生成有关。

关键词: 阿伐他汀, 心脏成纤维细胞, 内皮素-1, 心肌纤维化

Abstract: AIM: To investigate the effects of atorvastatin on the proliferation and collagen synthesis of cardiac fibroblasts (CFs) induced by endothelin-1 (ET-1). METHODS: Neonatal rat cardiac fibroblasts were randomly divided into 4 groups :control, ET-1, Atorvastatin, ET-1+atorvastatin (10^-7-10^-4 mol/L).CFs number was measured by MTT assay.Cell cycle distribution was determined with flow cytometer (FCM).[³H]-Proline uptake was evaluated by scinillation counting.Nitric Oxide (NO) was measured by chromatometry.RESULTS: 10^-6 mol/L ET-1 significantly increased the A490 value and [³H]-Pro incorporation, and decreased the secretion of NO compared with the control group (P<0.01).10^-7-10^-4 mol/L atorvastatin inhibited the above effects of ET-1 on CFs in a concentration-dependent manner (P<0.01 vs ET-1).In the ET-1 group, Phase S cell percentage was higher than that of contol, which was inhibited by atorvastatin (P<0.01 vs ET-1 and control).CONCLUSION: Atorvastatin dose-dependently inhibits the proliferation and collagen synthesis of cardiac fibroblasts induced by endothelin-1, which may be partially mediated by NO.

Key words: atorvastatin, cardiac fibroblasts, Endothelin-1, myocardial fibrosis

中图分类号:

R965.2

王艾丽, 陈玲玲, 胡剑峰, 程新耀. 阿伐他汀对内皮素-1 诱导的新生大鼠心肌成纤维细胞增殖和胶原合成的影响[J]. 中国临床药理学与治疗学, 2007, 12(9): 1058-1061.

WANG Ai-li, CHENG Ling-ling, HU Jian-feng, CHENG Xin-yao. Effects of atorvastatin on the proliferation and collagen synthesis of cardiac fibroblasts induced by endothelin-1[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(9): 1058-1061.

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