吡那地尔及二氮嗪对长期低氧大鼠肺动脉平滑肌KATP通道蛋白表达的影响
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Effects of Pinacidil and Diazoxide on protein level of ATP-sensitive potassium channels of pulmonary artery smooth muscles in chronic hypoxic rats
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    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(KATP) 蛋白表达的影响及KATP开放剂吡那地尔及二氮嗪的作用。方法:SD 雄性大鼠35只随机分成对照组、低氧组、吡那地尔干预组[吡那地尔2.0 mg/(kg·d),ig]、二氮嗪干预组[二氮嗪1.5 mg/(kg·d),ig]、5-羟癸酸(5-HD)+二氮嗪干预组[5-HD 3.0 mg/(kg·d),ig;二氮嗪1.5 mg/(kg·d),ig],每组7只。将低氧组和各干预组大鼠放入常压低氧舱内[O2(10.0% ± 0.5%)],每周6天,每天6 h 4周后测定平均肺动脉压(mPAP)并采用Western-blot技术,分析各组肺动脉主干平滑肌KATP蛋白表达。结果:①慢性低氧组大鼠的mPAP 显著高于正常对照组,吡那地尔干预组肺动脉压较低氧组显著下降,二氮嗪干预组加重慢性低氧所致的肺动脉压力升高,5-HD+二氮嗪干预组的mPAP显著低于二氮嗪干预组,P均 < 0.05。②低氧组调节亚基磺酰脲受体2B(SUR2B)蛋白水平显著低于正常组,吡那地尔干预组SUR2B 显著高于低氧组,二氮嗪干预组SUR2B蛋白水平显著低于低氧组,5-HD+二氮嗪干预组SUR2B显著高于二氮嗪干预组,与低氧组亦有显著统计学差异,P均 < 0.05。各组内向整流性孔区6.1(Kir6.1)蛋白没有显著差异(P < 0.05)。结论:慢性低氧抑制KATP通道蛋白的表达,而吡那地尔能提高表达,对慢性低氧所致的肺动脉高压和肺血管壁重构具有较好的预防和逆转作用;二氮嗪能加重低氧性肺动脉压升高,并抑制KATP通道蛋白的表达。

    Abstract:

    Objective:To study protein expression of ATP-sensitive potassium channels(KATP) of pulmonary artery in chronic hypoxic pulmonary artery hypertension(CHPAH) rats and in chronic hypoxic rats treated with KATP opener Pinacidil and Diazoxide. Methods:Thirty-five Sprague-Dawley(SD) male rats were randomly divided into five equal groups:control group,hypoxic group,Pinacidil group[2.0 mg/(kg·d),ig],Diazoxide group[1.5 mg/(kg·d),ig] and 5-HD+Diazoxide group[5-HD 3.0 mg/(kg·d),ig,Diazoxide 1.5 mg/(kg·d),ig]. Except the first group ,the other four groups were put into hypoxic and normobaric chamber[O2(10.0 ± 0.5)%] to establish chronic hypoxic model. Four weeks later,the mean pulmonary arterial pressure(mPAP) was measured. Western-blot was performed to analyze the protein level of KATP channels in pulmonary main artery smooth muscles. Results:①The level of mPAP was significantly higher in the hypoxic group than those in control group(P < 0.05). Pinacidil 2.0 mg/(kg·d) decreased the level of mPAP(mmHg) significantly. While Diazoxide 1.5 mg/(kg·d) increased the level of mPAP significantly. The level of mPAP was significantly lower in the 5-HD+Diazoxide group than those in Diazoxide 1.5 mg/(kg·d) group. ②The protein levels of SUR2B in the hypoxic group were significantly lower than those in the control group,and this decrease was partly reversed by Pinacidil. The protein levels of SUR2B in the Diazoxide group were significantly lower than those in the hypoxic group. The protein levels of SUR2B in the 5-HD+Diazoxide group were significantly higher than those in the Diazoxide group,and no difference in Kir 6.1 protein level was found among five groups. Conclusion:KATP channel protein expression was inhibited by chronic hypoxia,and this inhibition could be up-regulated by Pinacidil. Pinacidil might partly prevent the development of HPH and the pulmonary vascular remodeling;Diazoxide could aggravate the level of mPAP and down-regulate the protein expression of KATP channel.

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陈〓磊,解卫平,金〓宇,王 虹.吡那地尔及二氮嗪对长期低氧大鼠肺动脉平滑肌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):308-311315

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  • 收稿日期:2007-11-22
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