上海交通大学学报(医学版)

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Rock抑制剂法舒地尔改善高氧致新生大鼠肺纤维化的作用机制

漆秀洁1,2,李 静2,许 峰2,方 芳2   

  1. 1.重庆医科大学附属儿童医院 重庆市住院医师规范化培训基地 重庆市儿童发育重大疾病诊治与预防国际科技合作基地 儿科学重庆市重点实验室 儿童发育疾病研究教育部重点实验室, 重庆 400014; 2.重庆医科大学附属儿童医院儿科重症监护病房, 重庆 400014
  • 出版日期:2014-10-28 发布日期:2014-10-28
  • 通讯作者: 李 静, 电子信箱: lijingwangyi@126.com。
  • 作者简介:漆秀洁(1987—), 女, 硕士生; 电子信箱: 250931419@qq.com。
  • 基金资助:

    国家自然科学基金(81101442)

Mechanism of relieving hyperoxia-induced lung fibrosis of neonatal rats by Rock inhibitor fasudil

QI Xiu-jie1,2, LI Jing2, XU Feng2, FANG Fang2   

  1. 1.Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Training Base of Clinical Resident Standard Training in Chongqing, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; 2.Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University, Chongqing 400014, China
  • Online:2014-10-28 Published:2014-10-28
  • Supported by:

    National Natural Science Foundation of China, 81101442

摘要:

目的 探讨Rho激酶(Rock)抑制剂法舒地尔(FAS)改善高氧致新生大鼠肺纤维化的作用机制。方法 将24只SD新生大鼠,按随机数字表法分为空气组(正常对照组)、FAS空气组、高氧组和FAS高氧组,分别建立动物模型。在造模的第21日取各组新生大鼠行肺组织辐射状肺泡计数(RAC),Western blotting检测肺组织转化生长因子β1 (TGF-β1)蛋白及Rho/Rock信号通路中Rock1和磷酸化肌球蛋白轻链磷酸酶靶亚单位1 (p-MYPT1)蛋白的表达。结果 与空气组比较,高氧组RAC值明显下降(P<0.05); FAS高氧组RAC值较高氧组上升,但差异无统计学意义(P>0.05)。高氧组肺组织TGF-β1蛋白的表达较空气组显著升高(P<0.05),而FAS高氧组肺组织TGF-β1蛋白较高氧组明显降低(P<0.05)。与空气组比较,高氧组肺组织Rock1蛋白表达有上升趋势,但差异无统计学意义(P>0.05),而p-MYPT1蛋白表达明显升高(P<0.05); FAS高氧组肺组织Rock1蛋白表达较高氧组下降,但差异无统计学意义(P>0.05),而p-MYPT1蛋白表达明显降低(P<0.05)。结论 FAS可通过减少TGF-β1的表达,一定程度改善高氧致新生大鼠肺纤维化,其调控机制可能与抑制Rho/Rock信号通路的活化有关。

关键词: 高氧, 肺纤维化, 法舒地尔, 转化生长因子β1, Rho/Rock信号通路

Abstract:

Objective To investigate the mechanism of relieving hyperoxia-induced lung fibrosis of neonatal rats by the Rho kinase (Rock) inhibitor fasudil (FAS). Methods According to the random number tables, 24 Sprague-Dawley neonatal rats were randomly divided into the air group (control group), FAS air group, hyperoxia group, and FAS hyperoxia group. Animal models of each group were established. Rats were sacrificed after models were established for 21d. The radial alveolar count (RAC) was conducted for lung tissue. Expressions of transforming growth factor-β1 (TGF-β1) protein and Rock1 and myosin phosphatase target subunit-1 phosphorylation (p-MYPT1) proteins in Rho/Rock signaling pathway were detected by the Western blotting. Results Compared to the air group, the RAC of the hyperoxia group decreased significantly (P<0.05). The RAC of the FAS hyperoxia group increased compared to the hyperoxia group, but the difference was not statistically significant (P>0.05). Compared to the air group, the expression of TGF-β1 protein in pulmonary tissues of the hyperoxia group up-regulated significantly (P<0.05), while the expression of TGF-β1 protein in pulmonary tissues of the FAS hyperoxia group down-regulated significantly compared to the hyperoxia group (P<0.05). Compared to the air group, the expression of Rock1 protein in pulmonary tissues of the hyperoxia group tended to up-regulate, but the difference was not statistically significant (P>0.05), while the expression of p-MYPT1 protein up-regulated significantly (P<0.05). Compared to the hyperoxia group, the expression of Rock1 protein in pulmonary tissues of the FAS hyperoxia group down-regulated, but the difference was not statistically significant (P>0.05), while the expression of p-MYPT1 protein down-regulated significantly (P<0.05). Conclusion FAS can relieve hyperoxia-induced lung fibrosis of neonatal rats to a certain extent by downregulating the expression of TGF-β1. The regulation mechanism may be relevant to inhibiting the activation of Rho/Rock signaling pathway.

Key words: hyperoxia, lung fibrosis, fasudil, transforming growth factor-β1, Rho/Rock signaling pathway