埃他卡林对低氧诱导的肺动脉高压大鼠炎症反应的影响
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国家自然科学基金(81273571);江苏省人事厅六大人才高峰资助项目(2008074)


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    摘要:

    目的:研究ATP敏感性钾通道(KATP)开放剂埃他卡林(iptakalim,IPT)对低氧性肺动脉高压大鼠炎症反应的影响。方法:将96只清洁级SD大鼠随机分为对照(Control)组-低氧(Hypoxia)组-低氧+IPT(IPT)组,每组32只。Hypoxia组及IPT组每天置于常压低氧舱中8 h,每周6 d,持续4周。分别在低氧第1-2-3-4周末,各组随机取出8只大鼠测量右心室收缩压(RVSP),HE染色观察肺小动脉病理变化,抽取外周血,酶联免疫吸附法(ELISA)测定白细胞介素-1β(IL-1β)及IL-10,ED1+单核细胞免疫组化测定肺小动脉周围炎症细胞的浸润。结果:IPT可抑制大鼠慢性缺氧性RVSP升高-肺小动脉壁重构及其周围炎症细胞浸润;降低大鼠外周血及肺组织IL-1β含量,增加IL-10合成-释放。结论:IPT可能通过抑制肺血管炎症反应-降低RVSP-缓解肺血管重构,防治大鼠低氧性肺动脉高压。

    Abstract:

    Objective:To investigate the effects of iptakalim (IPT),an adenosine triphosphate (ATP)-sensitive potassium channel opener,on the inflammation of hypoxic pulmonary artery hypertension(HPAH) in rats. Methods:A total of 96 SD rats were randomly divided into three groups (the control group,the hypoxia group and the hypoxia + IPT group,n=32 for each group). Hypoxia-treated and IPT-treated rats were placed into normobaric hypoxia chamber for 4 weeks (8 h/day,6 days/week). Eight rats of each group were killed at the end of each week. The right ventricle systolic pressure (RVSP) was measured and the small pulmonary arterial morphologic changes were detected by HE staining. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the content of interleukin-1β (IL-1β) and IL-10. Immunohistochemisty for ED1+ monocytes was performed to detect inflammatory cells around pulmonary arterioles. Results:IPT significantly inhibited RVSP increasing induced by hypoxia the remodeling of small pulmonary artery wall and the infiltrating of the arounding inflammatory cells. Moreover,IPT prevented IL-1β increasing and IL-10 decreasing induced by hypoxia in both peripheral blood and lung. Conclusion:IPT can alleviate inflammation in pulmonary vascular,lower the RVSP,antagonize the proliferation and remodeling of the small pulmonary artery. It is a promising candidate for the treatment of HPAH.

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吴苏玲,解卫平,孔 辉,毕立清,朱 蓉.埃他卡林对低氧诱导的肺动脉高压大鼠炎症反应的影响[J].南京医科大学学报(自然科学版),2013,(2):149-154

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  • 收稿日期:2012-09-15
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  • 在线发布日期: 2013-03-05
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