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目的研究电压门控性钾通道亚型Kv2.1基因表达变化在大鼠低氧性肺动脉高压形成以及恢复中的作用。方法32只雄性SD大鼠均分为正常对照组、高原慢性低压低氧组(CH组)、二氯醋酸钠(DCA)治疗组(CH+DCA组)和高原低氧返回平原恢复7d组(CHR7组)。正常对照组在常压常氧平原条件下喂养,其余各组在模拟高原5000m低压氧舱内喂养21d,动物模型建成后用闭式胸腔法测平均肺动脉压(mPAP),荧光定量PCR法检测4组大鼠肺动脉平滑肌细胞(pulmonary arterial smooth muscle cells,PASMCs)的Kv2.1mRNA表达;免疫组织化学方法检测大鼠PASMCsKv2.1的表达;图像分析技术检测肺小动脉形态改变及Kv2.1表达强度变化;Westernblot法检测肺动脉平滑肌细胞Kv2.1蛋白表达。结果模拟高原5000m缺氧21d后,与正常对照组相比,CH组Kv2.1mRNA和蛋白表达明显下降,免疫组化显示PASMCsKv2.1表达的平均光密度值(mIOD)减少,而mPAP明显增高,肺小动脉管壁增厚,管腔狭窄,肺血管重构明显。与CH组相比,DCA+CH组和CHR7组Kv2.1mRNA和蛋白则明显恢复表达,PASMCsKv2.1表达的mIOD增加,mPAP下降,血管重构减弱。结论Kv2.1基因表达变化与高原低氧性肺动脉高压变化存在负相关性,表明Kv2.1在低氧性肺动脉高压的形成和恢复中可能起着一定的作用。
Objective To study the role of voltage-gated potassium channel subtypes Kv2.1 gene expression in the formation and recovery of hypoxic pulmonary hypertension in rats. Methods Thirty-two male Sprague-Dawley rats were randomly divided into normal control group, chronic hypoxia group (CH group), DCA group (CH + DCA group) and plateau hypoxia return plain CHR7 group). The normal control group was fed normoxia, and the rest were fed for 21 days in 5000m hypobaric chamber on the simulated plateau. After the animal model was established, the mean pulmonary artery pressure (mPAP) The expression of Kv2.1mRNA in PASMCs was detected by immunohistochemistry. The expression of Kv2.1 in rat PASMCs was detected by immunohistochemistry. The changes of Kv2.1 and Kv2.1 in the pulmonary arterial smooth muscle cells (PASMCs) Western blot was used to detect Kv2.1 protein expression in pulmonary artery smooth muscle cells. Results Compared with the normal control group, the expression of Kv2.1 mRNA and protein in CH group decreased significantly after hypoxia of 5000m simulated plateau for 21d. Immunohistochemistry showed that mIOD decreased and mPAP increased in PASMCs with reduced expression of Kv2.1, Pulmonary arterioles wall thickening, stenosis, pulmonary vascular remodeling obvious. Compared with CH group, Kv2.1 mRNA and protein of DCA + CH group and CHR7 group were significantly restored expression, PASMCsKv2.1 expression increased mIOD, mPAP decreased, vascular remodeling decreased. Conclusions There is a negative correlation between Kv2.1 gene expression and plateau hypoxic pulmonary hypertension, indicating that Kv2.1 may play a role in the formation and recovery of hypoxic pulmonary hypertension.