天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (2): 113-116.doi: 10.11958/j.issn.0253-9896.2015.02.001

• 缺氧与器官损伤 •    下一篇

间歇低氧对大鼠肺组织RhoA/ROCK通路及肺血管新生肌化的影响

杨晓琨，高梦丽，刘亚萌，李彩丽，曹洁△，冯靖△   

  1. 1. 天津医科大学总医院
    2. 天津医科大学总医院呼吸科
  • 收稿日期:2014-09-30 修回日期:2014-10-23 出版日期:2015-02-15 发布日期:2015-02-27
  • 通讯作者: 曹洁△，冯靖△ E-mail:tjyangxiaokun@126.com
  • 作者简介:杨晓琨(1988)，女，硕士在读，主要从事睡眠低氧性疾病研究
  • 基金资助:
    国家自然科学基金资助项目（81270144,30800507,81170071）

Effect of intermittent hypoxia on RhoA/ROCK pathway in lung and on the muscularization in pulmonary vascular in rat model

YANG Xiaokun, GAO Mengli, LIU Yameng, LI Caili, CAO Jie△, FENG Jing△   

  • Received:2014-09-30 Revised:2014-10-23 Published:2015-02-15 Online:2015-02-27

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摘要： 目的探讨间歇低氧（IH）对大鼠肺组织RhoA/ROCK 通路及肺血管新生肌化的影响。方法将40 只 Wistar 雄性大鼠随机分为对照组和IH 组各20 只，对照组：间歇正常氧暴露（21% O2）；IH 组：IH 暴露(5%~21% O2），持续4 周。暴露结束后，2 组均采用Real-time PCR 和Western blot 检测肺组织RhoA、ROCK mRNA 和蛋白表达情况，免疫组化法测定肺组织和肺动脉的增殖细胞核抗原（PCNA）及α-平滑肌肌动蛋白（SM-α-actin）的表达情况。结果IH 组肺组织RhoA mRNA（0.463±0.067 vs 0.182±0.040）、ROCK mRNA（0.384±0.062 vs 0.192±0.052）、RhoA 蛋白（0.827±0.065 vs 0.424±0.075）及ROCK 蛋白（0.488±0.088 vs 0.336±0.102）表达水平均高于对照组（均P <0.05）；IH 组肺组织PCNA[（54.67±1.80）% vs (9.14±0.91）%]、肺动脉PCNA[（49.40±1.21）% vs (8.38±1.13）%]、肺组织SM-α-actin （[ 42.66±1.63）% vs (35.44±1.41）%]与肺动脉SM-α-actin（[ 62.62±2.53）% vs (45.54±2.58）%]表达水平均明显高于对照组（均P <0.05）。结论RhoA/ROCK 传导通路在IH 所致肺动脉高压发病机制中可能起着重要作用；IH 可通过促进肺动脉的新生肌化进一步促进肺动脉压力升高。

关键词: 缺氧, 高血压, 肺性, 增殖细胞核抗原, 肌动蛋白类, 间歇低氧, 肺动脉高压, RhoA/ROCK

Abstract: Abstract:Objective To explore the effect of intermittent hypoxia (IH) on RhoA/ROCK pathway in lung and on the muscularization in pulmonary vascular in rat model. Methods Wistar rats (n=40) were randomly divided into two groups: the normal oxygen control group (n=20) and the IH group ( n=20). For 4 weeks, rats in control group and IH group were ex⁃ posed to intermittent normal oxygen (21% O2) or IH (5%-21% O2) respectively. Then, mRNA transcription and protein trans⁃ lation levels of RhoA/ROCK were examined by Real-time PCR and Western blot. Expression of proliferation cell nuclear an⁃ tigen (PCNA) and α-smooth muscle actin (SM-α-actin ) of lung and pulmonary artery were detected by immunohistochemis⁃ try. Results RhoA mRNA transcription level（0.463±0.067 vs 0.182±0.040）, ROCK mRNA transcription level（0.384± 0.062 vs 0.192±0.052）, RhoA protein expression level（0.827±0.065 vs 0.424±0.075）and ROCK protein expression level （0.488±0.088 vs 0.336±0.102）were higher in IH group than those in control group（P <0.05）；Levels of PCNA in lung tissue （[ 54.67±1.80）% vs (9.14±0.91）%], PCNA in pulmonary artery （[ 49.40±1.21）% vs (8.38±1.13）%], SM-α-actin in lung tis⁃ sue [（42.66±1.63）% vs (35.44±1.41）%] and SM-α-actin in pulmonary artery [（62.62±2.53）% vs (45.54±2.58）%] were also higher in IH group than those in control group（P <0.05）. Conclusion Rho/ROCK pathway may play an important role in developing pulmonary hypertension (PH) associated with IH; and IH can promote the muscularization in pulmonary vascular to accelerate PH.

Key words: anoxia, hypertension, pulmonary, proliferating cell nuclear antigen, actins, intermittent hypoxia, pulmonary hypertension, RhoA/ROCK