慢性低氧所致肺动脉高压对大鼠肺动脉内蛋白激酶Cα的膜转位和蛋白表达量的影响

摘要

Objective To investigate the changes of PKCα membrane translocation and protein expression levels in pulmonary arteries of hypoxia-induced pulmonary hypertension of rats,and therefore to explore the effect of PKCα in the development of hypoxia-induced pulmonary hypertension.Methods Male SD rats were randomly divided into six groups,and exposed to normoxia control or to normoxia hypoxia [(10 ± 0.1)％ oxygen] for 1,3,7,14 and 21 days to induced pulmonary hypertension.Right ventricle systolic pressure (RVSP) and right ventricle hypertrophy index (RVHI) were measured.Pulmonary tissues of rats were stained by hematoxylin-eosin (HE).The changes of PKCα membrane translocation and protein expression levels in pulmonary arteries were determined by using Western blot and Immunohistochemical stain.Results RVSP and RVHI weight ratio increased significantly under hypoxic exposures when compared with the normoxia control (P＜0.05).The pulmonary vascular walls of rats are obviously thickening after hypoxic exposure for 3,7,14 and 21 days.The protein expression levels of PKCα in pulmonary arteries decreased significantly at 1,3,7 and 14 days after hypoxic exposures when compared with that of normoxia control group (P ＜0.05).Conclusions The decrease of protein expression level of PKCα in pulmonary arteries may be involved in the development of hypoxia-induced rats pulmonary hypertension.%目的 通过观察慢性低氧所致肺动脉高压对大鼠肺动脉内蛋白激酶Cα(PKCα)的膜转位和蛋白表达量的影响,初步探讨PKCα在慢性低氧诱导大鼠肺动脉高压的发生和发展过程中所起的作用.方法 采用慢性常压低氧[氧浓度(10±0.1)％]大鼠肺动脉高压模型,将雄性SD大鼠随机分为正常对照组、低氧1d、3d、7d、14 d和21d组,检测大鼠右心室收缩压(RVSP)和右心室肥厚指数(RVHI),肺组织苏木精-伊红(HE)染色,应用蛋白免疫印迹和免疫组织化学的方法检测PKCα膜转位和蛋白表达水平的变化.结果 ①低氧1d、3d、7d、14 d和21d组与正常对照组相比,RVSP和RV/(LV+S)比值均明显增加(P＜0.05),低氧暴露3d、7d、14 d和21 d后大鼠肺动脉壁明显增厚;②PKCα的蛋白表达量在慢性低氧1d、3d、7d和14 d后比正常对照组明显下降(P＜0.05).结论 PKCα蛋白表达量的下调可能参与了慢性低氧诱导的大鼠肺动脉高压的发生和发展过程.