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 |
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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) |
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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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