环孢素A 改善异丙肾上腺素所致心肌损害和纤维化可能由抑制内皮素通路所介导

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (9): 966-971.

环孢素A 改善异丙肾上腺素所致心肌损害和纤维化可能由抑制内皮素通路所介导

彭洪军, 季晖, 戴德哉, 戴茵

中国药科大学药理研究室, 南京210009, 江苏

收稿日期:2008-08-02 修回日期:2008-09-21 出版日期:2008-09-26 发布日期:2020-10-13
通讯作者: 戴德哉, 男, 教授, 博士生导师, 研究方向:心血管药理学。Tel:025-83271270 E-mail:dezaidai@vip.sina.com
作者简介:彭洪军, 男, 博士研究生, 研究方向:心血管药理学。Tel:025-83271270 E-mail:hjp9595@126.com
基金资助:
国家自然科学基金项目(30670760)

Protective effects of cyclosporine A on myocardial damage and fibrosis induced by isoproterenol via ET pathway

PENG Hong-jun, JI Hui, DAI De-zai, DAI Yin

Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China

Received:2008-08-02 Revised:2008-09-21 Online:2008-09-26 Published:2020-10-13

摘要/Abstract

摘要： 目的:研究环孢素A(Cyclosporine A, CsA)对异丙肾上腺素(isoproterenol, Iso) 诱导心肌损害和纤维化的改善, 探讨内皮素通路在其过程中的作用。方法:SD 大鼠给予Iso(2 mg°kg^-1°d^-1, s.c.) 10 d, 建立大鼠心肌损害和纤维化病变。CsA治疗组预先给予CsA (25 mg/kg, s.c.) 一次。结果:Iso 损害心肌, 引起心功能下降, 使左室心肌中羟脯氨酸(hydroxyproline, Hyp) 含量增高, 内皮素-1(ET-1) 及受体(ETA R)、结缔组织生长因子(CTGF)和基质金属蛋白酶-9(MMP-9) mRNA 和蛋白表达上调。CsA 明显改善心功能, 降低Hyp 含量, 减轻升高的mRNA 和蛋白表达。结论:CsA 改善Iso引起的大鼠心功能损害和纤维化, 与抑制内皮素通路相关。

关键词: 环孢素A, 内皮素-1, 内皮素受体A, 结缔组织生长因子, 基质金属蛋白酶-9

Abstract: AIM: To investigate the protective effects of Cyclosporine A (CsA) on myocardial damage and fibrosis induced by isoproterenol (Iso) in rats and the role of ET pathway.METHODS: Myocardial damage and fibrosis in rats were produced by isoproterenol (2 mg°kg^-1 °d^-1, s.c.) for 10 days.In CsAtreated group, the rats were pretreated by CsA (25 mg/kg, s.c.).All the animals were subjected to cannulation through left carotid artery to measure LVSP, LVEDP, and±dp dtmax under urethane anesthesia. The contents of hydroxyproline (Hyp) in the left ventricle was assayed.The expressions of ET-1, ETAR, CTGF and MMP-9 mRNA were measured by RT-PCR and ETAR and MMP-9 protein were measured by western blotting.RESULTS: Compared with the control group, impaired cardiac function, elevated Hyp, and upregulation of ET-1, ETAR, CTGF and MMP-9 in mRNA and ETAR and MMP-9 in protein were found in Iso treated group.Pretreatment with CsA these changes were attenuated.CONCLUSION: CsA can alleviate myocardial damage and fibrosis induced by Iso in rats, and this effect is, at least in part, mediated by the ET pathway.

Key words: CyclosporineA, endothelin-1, endothelinAreceptor, connectivetissuegrowthfactor, matrixmetalloproteinase9

中图分类号:

R965.2

彭洪军, 季晖, 戴德哉, 戴茵. 环孢素A 改善异丙肾上腺素所致心肌损害和纤维化可能由抑制内皮素通路所介导[J]. 中国临床药理学与治疗学, 2008, 13(9): 966-971.

PENG Hong-jun, JI Hui, DAI De-zai, DAI Yin. Protective effects of cyclosporine A on myocardial damage and fibrosis induced by isoproterenol via ET pathway[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(9): 966-971.

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