低氧肺动脉高压大鼠蛋白激酶CβⅡ蛋白表达及膜转位水平的变化

Changes of PKCβⅡ Protein Expression and Membrane Translocation in Pulmonary Artery of Rats with Hypoxic Pulmonary Hypertension

目的 建立慢性低氧性肺动脉高压大鼠模型并初步探讨蛋白基酶CβⅡ（PKCβⅡ）在慢性低氧性肺动脉高压的发生发展过程中所起的作用.方法 建立慢性常压低氧肺动脉高压大鼠模型,将清洁级SD大鼠,随机分为正常对照组、低氧1d、3d、7d、14d和21d组,检测大鼠右心室收缩压（right ventricle systolic pressure,RVSP）和右心室肥厚指数（right ventricle hypertrophy index,RVHI）,采用HE染色观察肺动脉病理学改变,Western blotting方法检测大鼠肺动脉内PKCβⅡ蛋白表达和膜转位水平的变化.结果 （1）与正常对照组相比,低氧暴露1d、3d、7d、14d、21d后RVSP均明显上升（P＜0.05）; RVHI低氧3d、7d、14d、21 d组较正常对照组明显上升（P＜0.05）;低氧暴露3、7和21 d组肺动脉病理学改变明显.（2）PKCβⅡ蛋白的表达量在慢性低氧3d、7d、14d和21 d与正常对照组相比明显降低（P＜0.05）,慢性低氧3d后PKCβⅡ膜转位水平较正常对照组明显下降（P＜0.05）.结论 PKCβⅡ蛋白表达和膜转位水平的下调可能参与了大鼠慢性低氧性肺动脉高压的发生和发展过程.

Objective To establish rats model of chronic pulmonary hypertension （PH） and preliminarily explore the effect of PKC（a）Ⅱ in the development of hypoxia-induced pulmonary hypertension.Methods Male SD rats were exposed to normobaric hypoxia to induce PH model.The rats were randomly divided into six groups,and exposed to normoxia control and to normoxia hypoxia for 1 d,3 d,7 d,14 d and 21 d.Right ventricle systolic pressure （RVSP） and right ventricle hypertrophy index（RVHI） were measured.Pathological changes of the pulmonary arteries were observed by HE staining.The changes of PKCβⅡ protein expression and membrane translocation in pulmonary arteries were also detected by Western blotting.Results RVSP increased significantly after hypoxic exposure for 1 d,3 d,7 d,14 d and 21 d when compared with the normoxia control（P＜0.05）; There were significant rise in RVHI after hypoxic exposure for 3 d,7 d,14 d and 21 d （P＜0.05）.The pathological changes of the pulmonary arteries were significant at 3 d,7 d,21 d.PKC（a）Ⅱ protein expression decreased significantly at 3 d,7 d,14 d,21 d after chronic hypoxia than those of normal control groups respectively （P＜0.05）.Significant decrease of PKCβⅡ membrane translocation level in pulmonary arteries of rats could be detected after hypoxic exposure 3 d（P＜0.05）.Conclusion The decrease in protein expression and membrane translocation of PKCβⅡ may be involved in the development of the chronic hypoxiainduced pulmonary hypertension.