埃他卡林对长期低氧大鼠肺动脉平滑肌KATP mRNA 的影响

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (4): 389-393.

埃他卡林对长期低氧大鼠肺动脉平滑肌K_ATP mRNA 的影响

沈红^1,2, 王虹¹, 解卫平^1,2, 胡刚²

¹南京医科大学第一附属医院呼吸内科, 南京210029, 江苏;
²南京医科大学药理和神经生物学系, 南京210029, 江苏

收稿日期:2003-10-28 修回日期:2003-12-24 出版日期:2004-04-26 发布日期:2020-11-20
通讯作者: 胡刚, 男, 博士, 博士生导师, 研究方向为分子药理学与临床药理学的研究。Tel:025-6663108 Fax:025-6508960 E-mail:ghu@njmu.edu.cn
作者简介:沈红, 女, 在读硕士, 研究方向:低氧性肺动脉高压。
基金资助:
江苏省科委社会发展基金项目(№BJ200051);江苏省教育厅基金项目(№OOKJB320009)

Effects of Iptkalim hydrochloride on mRNA level of ATP-sensitive potassium channels of pulmonary artery smooth muscles in chronic hypoxic rats

SHEN Hong^1,2, WANG Hong¹, XIE Wei-Ping^1,2, HU Gang²

¹Department of Pulmonology, theFirst Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China;
²Department of Pharmacology &Neurobiology, Nanjing Medical University, Nanjing 210029, Jiangsu, China

Received:2003-10-28 Revised:2003-12-24 Online:2004-04-26 Published:2020-11-20

摘要/Abstract

摘要： 目的:研究慢性低氧对大鼠肺动脉平滑肌ATP 敏感钾通道(K_ATP) mRNA 表达的影响及新型K_ATP开放剂盐酸埃他卡林的作用。方法:SD 雄性大鼠16 只随机分成对照组、低氧组、低剂量治疗组(盐酸埃他卡林0.75 mg·kg^-1 ·d^-1, ig)、高剂量治疗组(盐酸埃他卡林1.5 mg·kg^-1·d^-1, ig) 。将低氧组和治疗组大鼠放入常压低氧舱制备动物模型;采用RT-PCR 技术, 分析各组肺动脉主干平滑肌K_ATP mRNA表达。结果:低氧组SUR2 mRNA 水平显著低于正常组, 高剂量治疗组SUR2 显著高于低氧组, 各组Kir 6.1 没有显著差异。结论:慢性低氧抑制K_ATP 通道表达, 而盐酸埃他卡林能提高表达, 可从肺动脉高压发病机制上理解该药物治疗价值。

关键词: ATP 敏感钾通道, 低氧性肺动脉高压, 盐酸埃他卡林, 肺动脉平滑肌, mRNA, RT-PCR

Abstract: AIM: To study mRNA expression of ATP-sensitive potassium channels (K_ATP) of pulmonary artery in chronic hypoxic pulmonary artery hypertension (CHPAH) rats and in chronic hypoxic rats treated with novel K_ATP opener Iptkalim hydrochloride.METHODS: Sixteen Sprague-Dawley(SD) male rats were randomly divided into control group, hypoxic group, low dose Iptkalim group (0.75 mg·kg^-1·d^-1), and high dose Ipkalim group (1.5 mg·kg^-1 ·d^-1).Except the first group, the other three groups were put into hypoxic and normobaric chamber to establish chronic hypoxic model.Four weeks later, reverse transcription polymerase chain reaction (RT-PCR) was performed to analyze the mRNA level of K_ATP channels in pulmonary main artery smooth muscles. RESULTS: The mRNA levels of SUR2 in the hypoxic group were significantly lower than those in the control group, this decrease was completely reversed by Iptkalim in high dose group, and no difference in Kir 6.1 mRNA level was found between four groups.CONCLUSION: K_ATP channel transcriptional expression is inhibited by chronic hypoxia, and this inhibition can be up-regulated by Iptkalim.The role of potassium channel in the development of CHPAH may explain the therapeutic mechanism of Iptkalim.

Key words: ATP-sensitive potassium channel, chronic hypoxic pulmonary artery hypertension, Iptkalim hydrochloride, pulmonary artery smooth muscle, mRNA, RT-PCR

中图分类号:

R965.1

沈红, 王虹, 解卫平, 胡刚. 埃他卡林对长期低氧大鼠肺动脉平滑肌K_ATP mRNA 的影响[J]. 中国临床药理学与治疗学, 2004, 9(4): 389-393.

SHEN Hong, WANG Hong, XIE Wei-Ping, HU Gang. Effects of Iptkalim hydrochloride on mRNA level of ATP-sensitive potassium channels of pulmonary artery smooth muscles in chronic hypoxic rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(4): 389-393.

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