埃他卡林对ET-1诱导的人肺动脉平滑肌细胞KATP通道蛋白表达的影响
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Effects of Iptakalim on the expression of KATP protein in cultured human pulmonary artery smooth muscle cells induced by endothelin-1
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    摘要:

    目的:研究新型ATP敏感性钾通道(KATP)开放剂埃他卡林对内皮素-1(ET-1)诱导的人肺动脉平滑肌细胞(HPASMCs)上KATP蛋白表达的影响。方法:原代培养人肺动脉平滑肌细胞,随机分成对照组,ET-1组,ET-1+埃他卡林组,ET-1+吡那地尔组,ET-1+埃他卡林+格列本脲组,ET-1+ 吡那地尔+格列本脲组,用Western-blot方法分析各组KATP蛋白磺酰脲受体亚单位(SUR2B)和内向整流性孔区亚单位(Kir6.1)表达变化情况。结果:与ET-1的作用相反,埃他卡林能使ET-1诱导下的SUR2B亚基表达升高,特异性KATP阻断剂格列本脲可逆转埃他卡林引起的SUR2B亚基表达升高;但各组对Kir6.1亚基表达无明显影响。结论:埃他卡林通过上调KATP的SUR2B亚基表达而发挥其在治疗低氧性肺动脉高压(HPH)中的作用,可望成为治疗低氧性肺动脉高压的新药。

    Abstract:

    Objective:To investigate the effects of Iptakalim,a novel ATP-sensitive potassium channel opener(KATPCO),on the expression of ATP-sensitive potassium channel(KATP) protein in cultured human pulmonary artery smooth muscle cells(HPASMCs) induced by endothelin-1(ET-1). Methods:By Western- blot analysis,the expression of both SUR2B and Kir6.1,subunits of KATP protein,was detected in primary cultured HPASMCs,which were randomly divided into control group,ET-1 group,ET-1+ Iptakalim group,ET-1+ Pinacidil group,ET-1+ Iptakalim+ Glibenclamide group and ET-1+ Pinacidil+ Glibenclamide group. Results:Compared with ET-1,Iptakalim could upregulate the SUR2B subunit expression,which could be inhibited by Glibenclamide,a particular ATP-sensitive potassium channel blocker. However,there was no significant difference in Kir6.1 subunit expression in each group. Conclusion:Iptakalim,a new potential candidate in the treatment of hypoxic pulmonary hypertension(HPH),could play an important role by upregulating the expression of SUR2B subunit.

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何志成,张石江,朱煜明,汤纳平,王〓虹,解卫平,倪布清,章〓斌.埃他卡林对ET-1诱导的人肺动脉平滑肌细胞KATP通道蛋白表达的影响[J].南京医科大学学报(自然科学版),2008,28(3):304-307

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  • 收稿日期:2007-10-22
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