文章摘要
牛梦婕 李瑛 杭天星 李惟捷 徐淑娣 邹远康 李圣青.罗格列酮对低氧性肺动脉高压大鼠PPARr和PTEN 表达的影响[J].,2016,16(17):3217-3222
罗格列酮对低氧性肺动脉高压大鼠PPARr和PTEN 表达的影响
Effect of Rosiglitazone on Expression of PPARr and PTEN in Rats withHypoxia-induced Pulmonary Hypertension
  
DOI:
中文关键词: PPAR-r  PTEN  低氧性肺动脉高压  细胞增殖
英文关键词: PPAR-r  PTEN  Hypoxic pulmonary hypertension  Cell proliferation
基金项目:国家自然科学基金项目(81470249)
作者单位
牛梦婕 李瑛 杭天星 李惟捷 徐淑娣 邹远康 李圣青 第四军医大学西京医院呼吸内科陕西省人民医院呼吸内科西安市第九医院呼吸内科 
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中文摘要:
      目的:研究罗格列酮(rosiglitazone, RSG)对低氧性肺动脉高压大鼠过氧化物酶体增殖物激活受体-r(Peroxisome proliferator activated receptor gamma, PPAR-r)和10 号染色体缺失张力蛋白同源磷酸酶基因(Phosphatase and tensin homolog deleted on chromosome 10, PTEN)表达的影响。方法:SD 大鼠随机分为正常对照组、低氧组、低氧+ 罗格利酮组,建立低氧性肺动脉高压大鼠模 型,4 周后测定各组大鼠右心室压力、右心肥厚指标,同时检测各实验组PPAR-r、PTEN 的表达和组织病理学变化。培养原代大鼠 肺动脉平滑肌细胞,分别给与低氧、低氧+罗格列酮、低氧+GW9662 处理后观察细胞增殖及PPARr、PTEN 的表达变化。结果:① 与正常组相比,低氧组大鼠右心室压力、右心肥厚指标明显增加,肺小动脉管壁增厚,PPAR-r、PTEN 的表达明显减少。与低氧组相 比,低氧+罗格列酮组大鼠右心室压力下降,右心室及肺小动脉管壁的肥厚减轻,PTEN 的表达增加。②低氧下,PASMCs 中 PPARr、PTEN表达明显减低,细胞增殖较常氧明显增加,给与罗格列酮后,PTEN 表达增加,给与GW9662,PTEN表达减少。③罗 格列酮可以抑制PASMCs低氧下的增殖,而给与GW9662 后,这一抑制作用减轻。结论:早期应用罗格列酮可激活低氧性肺动脉 高压大鼠PPARr的活性,进而上调PTEN表达,改善低氧性肺动脉高压。
英文摘要:
      Objective:To investigate the effects of Rosiglitazone, the agonist of PPAR-r, on expression of PPAR-r and PTEN , on hypoxia-induced pulmonary hypertension in rats.Methods:Eighteen rats were randomly divided into 4 groups: normal control group, hypoxia group and hypoxia + rosiglitazone group. All rats except the normal control group were exposed to a hypobaric hypoxia chamber for 4 weeks to establish hypoxia pulmonary hypertension model. After the treatments, the mean right ventricular pressure (mRVP), the right ventricular to the left ventricle and interventricular septum (RV/LV+S), the right ventricle to body weight ratio (RV/BW) and small pulmonary artery rings were measured. Also, the expression of PPAR-r and PTEN were detected. In vivo, pulmonary artery smooth muscle cell were cultured respectively in normoxia, hypoxia, hypoxia+ rosiglitazone and hypoxia+ GW9662. And then the expression of PPAR-r and PTEN, the cell proliferation of PASMCs were detected.Results:① Compared with normal control group, mRVP, RV/ (LV+S), RV/BW and small pulmonary artery rings were increased significantly in hypoxia group. And the expression of PPAR-r and PTEN were decreased. In hypoxia+ rosiglitazone group, mRVP, RV/ (LV+S), RV/BWand small pulmonary artery rings were decreased compared to hypoxia group. On the contrary, the expression of PTEN increased. ② Compared with normoxia group, the expression of PPAR-rand PTEN were reduced in hypoxia group, increased in hypoxia+ rosiglitazone group and decreased in hypoxia+GW9662 group. ③ PASMCs in hypoxia had increased proliferation compared to normoxia. And rosiglitazone inhibits the increased proliferation of PASMCs in hypoxia. Also the anti-proliferation effect of rosiglitazone were decreased in hypoxia+RSG+GW9662 group.Conclusion:Early use of rosiglitazone upregulates the expression of PPAR-r and PTEN, thereby ameliorating hypoxia induced hypertension in rats.
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