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目的研究电压门控性钾通道亚型(Kv1.5)在高原低压低氧性肺动脉高压中的作用,观察二氯醋酸钠(DCA)对高原低压低氧性肺动脉高压大鼠肺小动脉平滑肌细胞(PASMCs)电压门控性钾通道Kv1.5亚型基因表达的影响和肺动脉高压的降压作用。方法24只雄性SD大鼠随机分为正常对照组(N组,8只)、高原低压低氧组(HA组,8只)及DCA干预组(DCA组,8只)。N组置于平原处室内喂养,HA组和DCA组均同时置于模拟的海拔5000m高原环境,DCA组大鼠予以DCA70mg·kg-1·d-1灌胃。21d后测量三组大鼠平均肺动脉压(mPAP)、肺小动脉平滑肌和心脏壁厚度,用荧光定量PCR法检测三组大鼠PASMCs Kv1.5 mRNA,免疫组织化学和免疫印迹法观察大鼠PASMCsKv1.5蛋白的表达。结果模拟高原5000m21d后,HA组大鼠mPAP明显高于N组(P<0.01),其肺小动脉管壁增厚,管腔狭窄,表现为管壁厚度占外径的百分比(WT%)、管壁面积占总面积的百分比(WA%)和右心室与左心室加室间隔之比(RV/LV+S)较N组明显升高(P均<0.01)。与HA组相比,DCA组mPAP则明显降低(P<0.01),表现血管重构减弱,WT%和WA%明显下降(P<0.01),RV/LV+S下降(P<0.01)。HA组Kv1.5 mRNA明显低于N组(P<0.01),DCA组Kv1.5 mRNA则明显恢复表达(P<0.01)。HA组肺小动脉壁Kv1.5平均光密度低于N组(P<0.01),DCA组则明显高于HA组(P<0.01)。蛋白表达呈现相似结果。结论高原低压低氧性大鼠PASMCs Kv1.5表达明显受到抑制,DCA具有恢复Kv1.5表达、阻止肺小动脉重塑及降低肺动脉压的作用。
Objective To investigate the effect of voltage-gated potassium channel subtypes (Kv1.5) on hypobaric hypobaric hypoxic pulmonary hypertension (HAPH) and to observe the effect of sodium dichloroacetate (DCA) on pulmonary arteriolar smooth muscle cells (PASMCs) on the voltage-gated potassium channel Kv1.5 subtype and the hypotensive effect of pulmonary hypertension. Methods Twenty-four male SD rats were randomly divided into normal control group (n = 8), plateau hypobaric hypoxia group (HA group, n = 8) and DCA intervention group (n = 8). N group was placed in the plains at home feeding, HA group and DCA group were simultaneously placed in a simulated altitude of 5000m plateau environment, DCA group to DCA70mg · kg-1 · d-1 gavage. The mean pulmonary arterial pressure (mPAP), pulmonary arteriole smooth muscle and heart wall thickness were measured after 21 days in rats. Kv1.5 mRNA expression in PASMCs was detected by real-time PCR. Immunohistochemistry and Western blotting were used to detect the expression of Kv1 .5 protein expression. Results After mimicking the plateau of 5000m21d, the mPAP in HA group was significantly higher than that in N group (P <0.01). The pulmonary arteriole thickening and lumen stenosis were observed in HA group. The percentage of wall thickness to outer diameter (WT%), The ratio of wall area to total area (WA%) and RV / LV + S ratio was significantly higher than that of N group (all P <0.01). The mPAP in DCA group was significantly lower than that in HA group (P <0.01), which indicated that the remodeling of vascular remodeling was weakened, the percentages of WT% and WA% decreased significantly (P <0.01), and RV / LV + S decreased (P <0.01). Kv1.5 mRNA in HA group was significantly lower than that in N group (P <0.01), and Kv1.5 mRNA in DCA group was significantly restored (P <0.01). The average optical density of Kv1.5 in HA group was lower than that in N group (P <0.01), while that in DCA group was significantly higher than that in HA group (P <0.01). Protein expression showed similar results. Conclusion The expression of Kv1.5 in PASMCs is significantly inhibited in plateau hypoxic hypoxic rats. DCA can restore the expression of Kv1.5, prevent the remodeling of pulmonary arterioles and decrease the pulmonary arterial pressure.