地塞米松抑制慢性心衰大鼠心肌中内皮素信号通路的过度激活而改善心肌纤维化

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (4): 392-395.

地塞米松抑制慢性心衰大鼠心肌中内皮素信号通路的过度激活而改善心肌纤维化

纳涛, 戴德哉, 汤晓赟, 戴茵

中国药科大学药理研究室, 南京210009, 江苏

收稿日期:2006-07-31 修回日期:2006-07-31 发布日期:2020-10-30
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-mai l:dezaidai@vip.sina.com
基金资助:
国家自然科学基金资助项目(30572193)

Dexamethasone suppressed over-activated endothelin system in chronic heart failure rats via anti-oxidative stress effect

NA Tao, DAI De-zai, TANG Xiao-yun, DAI Yin

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

Received:2006-07-31 Revised:2006-07-31 Published:2020-10-30

摘要/Abstract

摘要： 目的观察地塞米松对慢性心衰大鼠心肌中内皮素(ET) 信号通路的过度激活与氧化应激的干预作用。方法雄性SD 大鼠, 通过冠脉结扎6 周造成慢性心衰模型。分为慢性心衰组、地塞米松组, 另设假手术组作为阴性对照。地塞米松组动物在饮水中按1 μg mL 的浓度给予地塞米松治疗。连续治疗6 周后, 取心脏进行Masson 三色法染色, 以检测心肌纤维化;RT-PCR 法检测心肌组织中ETA 受体、NF-κB和一氧化氮合酶(iNOS) 的基因表达水平。结果与假手术组相比, 慢性心衰组大鼠心肌纤维化显著, 地塞米松能有效改善心衰大鼠心肌组织的纤维化;心衰大鼠心肌组织中ETA 受体、NF-κB 和iNOS 的基因表达水平明显上调, 而地塞米松可使心衰大鼠心肌中ETA 受体、NF-κB 和iNOS 的基因表达水平显著下调。结论地塞米松通过下调ETA 受体, 抑制ET 信号通路的过度激活和抗氧化作用, 有效改善慢性心衰大鼠的心肌纤维化。

关键词: 地塞米松, 氧化应激, 内皮素, ETA 受体, 核因子-κB, 一氧化氮合酶, 慢性心衰

Abstract: AIM: To investigat over-activated endothelin (ET) signaling and oxidative stress in chronic heart failure (CHF) rats and dexamethasone intervention. METHODS: Rats were performed left coronary artery ligation for 6 weeks to develop CHF and treated with dexamethasone.Masson's trichrome was used to measure myocardial fibrosis.mRNA expression of endothelin A receptor (ETA R), NF-κB and inducible nitric oxide synthase (iNOS) in myocardium were performed. RESULTS: Myocardial fibrosis was more obvious in CHF group than that in sham operation group.Dexamethasone treatment ameliorated interstitial fibrosis in myocardium of CHF rats.mRNA expression of ETAR, NF-κB and iNOS in myocardium of CHF rats was significantly upregulated compared with sham operation group, and dexamethasone down-regulated the mRNA expression of ETAR, NF-κB and iNOS. CONCLUSION: Dexamethasone inhibits over-activated ET signaling and oxidative stress in CHF myocardium through the down-regulated ETAR, which attenuate myocardial fibrosis.

Key words: dexamethasone, oxidative stress, endothelin, endothelin A receptor, NF-κB, nitricoxide synthase, chronic heart failure

中图分类号:

纳涛, 戴德哉, 汤晓斌贝, 戴茵. 地塞米松抑制慢性心衰大鼠心肌中内皮素信号通路的过度激活而改善心肌纤维化[J]. 中国临床药理学与治疗学, 2007, 12(4): 392-395.

NA Tao, DAI De-zai, TANG Xiao-yun, DAI Yin. Dexamethasone suppressed over-activated endothelin system in chronic heart failure rats via anti-oxidative stress effect[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(4): 392-395.

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