Objective To explore the effects of chronic hypoxia on the expression of p27 and Skp2 in pulmonary artery and elucidate the underlying mechanism for hypoxic pulmonary hypertension ( HPH) . This study may provide new strategies for clinical treatment of HPH. Methods SD rats were assigned into 2 groups: control group and hypoxia group ( with chronic hypoxia exposure for 4 weeks) .Then we got the hypoxic pulmonary hypertension rat models. Hemodynamic and pulmonary pathomorphology data were gathered. Western blotting or reverse transcriptional polymerase chain reaction (RT - PCR) were adopted to test p27, Skp2 changes in rat pulmonary artery. Results Chronic hypoxia down - regulated the expression of p27 and up - regulated the expression of Skp2.Conclusion Chronic hypoxia markedly elevates the expression of Skp2 and decreases the expression of p27 in rat pulmonary artery. Increasing the expression of p27 or inhibiting the production of Skp2 might provide new therapeutic strategies for HPH treatment.%目的 研究慢性低氧对细胞周期抑制蛋白p27及S期蛋白相关激酶2的影响,探讨低氧性肺动脉高压的机制.方法 复制慢性低氧性肺动脉高压大鼠模型,将大鼠分为常氧对照组(Normoxia)和低氧模型组(Hypoxia)两组.待模型复制完毕后,测定大鼠RVPSP和RV/LV+S,然后进行组织病理分析,测定MA%和MT%.利用Western-blot实验和RT-PCR实验检测p27、Skp2蛋白及RNA水平的变化.结果 慢性低氧显著增加大鼠RVPSP、RV/LV+S、MA%和MT%,引起大鼠肺动脉压力增高、右心室肥厚和肺中小动脉中膜增厚及外膜增生.Western-blot实验发现,低氧组大鼠肺动脉中p27蛋白表达显著减少,Skp2蛋白表达上调.结论 慢性低氧导致Skp2表达升高,p27表达减少.p27表达减少而对平滑肌细胞抑制作用减弱,进而导致细胞增殖.因此,把p27或Skp2作为靶点可能为治疗低氧性肺动脉高压提供新的思路.
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