埃他卡林对慢性低氧大鼠肺动脉血管内皮生长因子mRNA和蛋白表达的影响
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国家自然科学基金资助项目(30871139);省科技厅基础研究计划(自然科学基金)资助项目(BK2006246);南京市社会发展项目(200701106)


Effects of iptakalim on the mRNA and protein expression of VEGF in the pulmonary artery of claronically hypoxic rats
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    目的:研究新型ATP敏感性钾通道开放剂埃他卡林(IPT)对低氧性肺动脉高压(HPH)大鼠肺动脉血管内皮生长因子(VEGF)表达的影响-方法:雄性SD大鼠36只随机分成对照组-HPH模型组-IPT干预组,每组12只-IPT干预组给予IPT 1.5 mg/(kg·d)灌胃,对照组及HPH模型组给予0.9% NaCl 5 ml/(kg·d)灌胃-HPH组及IPT干预组在(10.0 ± 0.5)%氧浓度下饲养,每天8 h,每周6天,4周时测定平均肺动脉压(mPAP)-RV/(LV+S),逆转录聚合酶链式反应(RT-PCR)和Western-blot技术检测各组肺动脉主干VEGF mRNA和蛋白的表达-结果:① HPH模型组大鼠mPAP和RV/(LV+S)显著高于对照组(P < 0.01),IPT干预组mPAP和RV/(LV+S)较HPH模型组显著下降(P < 0.01)-②HPH模型组大鼠肺动脉VEGF mRNA及蛋白表达高于对照组,两者具有显著统计学意义(P < 0.01),IPT干预组与HPH模型组比较,VEGF mRNA及蛋白表达均下降(P < 0.01);IPT干预组与对照组比较,VEGF mRNA及蛋白表达差异无显著性(P > 0.05)-结论:HPH模型大鼠肺动脉VEGF mRNA及蛋白表达增加,IPT可明显抑制慢性低氧大鼠肺动脉VEGF mRNA和蛋白的表达-

    Abstract:

    Objective:To study the effects of a new ATP-sensitive potassium channel opener, iptakalim(IPT), on the mRNA and protein expression of vascular endothelial growth factor(VEGF) in the pulmonary artery of rats with hypoxic pulmonary hypertension (HPH). Methods:Thirty-six Sprague-Dawley(SD) male rats were randomly divided into three equal groups:the control group and hypoxic group were given 5 ml/(kg·d) 0.9% sodium chloride,ig; the treated group were given 1.5 mg/(kg·d)] IPT,ig. excepting the first group, the other two groups were put into hypoxic and normobaric chamber[(10.0 ± 0.5)%O2, 8 h/day and 6 day/week] to establish a chronic hypoxic model. After four weeks, the mean pulmonary arterial pressure(mPAP), right ventricle/left ventricle and septum[RV/(LV+S)] were measured. RT-PCR and Western-blot were performed to analyze the mRNA and protein level of VEGF in the main pulmonary artery. Result:①The levels of mPAP and RV/(LV+S) were significantly higher in the hypoxic group than those in the control group(P < 0.01). Iptakalim 1.5 mg/(kg·d) decreased the levels of mPAP and RV/(LV+S)(P < 0.01).②The mRNA and protein levels of VEGF in the hypoxic group were significantly higher than those in the control group(P < 0.01). The trented group significantly decreased VEGF mRNA and protein expression compared with those in the hypoxic group(P < 0.01). There were no differences in VEGF mRNA and protein levels between the control group and the treated group(P > 0.05). Conclusion:IPT 1.5 mg/(kg·d) remarkably inhibited the levels of VEGF mRNA and protein expression compared with the hypoxic group.Iptakalim is a promising candidate for the treatment of hypoxic pulmonary hypertension.

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王 珏,陈建波,解卫平,金 宇,王 虹.埃他卡林对慢性低氧大鼠肺动脉血管内皮生长因子mRNA和蛋白表达的影响[J].南京医科大学学报(自然科学版),2009,29(4):425-428434

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  • 收稿日期:2008-11-05
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