RhoA/Rho激酶及其抑制剂对COPD大鼠气道重塑的影响  

The effects of RhoA/Rho kinase and its inhibitor on airway remodeling of COPD rats

作　　者：黄健莹[1] 梁健健[2] 钟维农[1] 陈振宇[3] 

机构地区：[1]广州市第一人民医院内科,广州510180 [2]广州市第一人民医院药剂科,广州510180 [3]广州市第一人民医院检验科,广州510180

出　　处：《广州医药》2014年第4期27-30,共4页Guangzhou Medical Journal

摘　　要：目的观察慢性阻塞性肺疾病(COPD)大鼠模型肺组织RhoA,ROCKⅡ含量的变化,探讨Y-27632对COPD大鼠RhoA/Rho激酶(ROCK)信号通路的调控及其对气道重塑的影响。方法将60只清洁级Wister雄性大鼠按随机数字表法分成3组,即正常对照组、COPD模型组和Y-27632干预组,每组20只,采用烟熏及气管滴入脂多糖(LPS)法建立COPD大鼠模型,用ROCK特异性抑制剂Y-27632进行干预,测定大鼠的肺功能,光镜观察肺组织结构,用医学图像分析软件测定支气管管壁厚度(Wat/Pbm)和气道平滑肌厚度(Wam/Pbm),反映气道重塑的程度。免疫组化法测定肺组织ROCKⅡ蛋白的表达,RT-PCR法测定RhoA、ROCKⅡmRNA含量。结果①与对照组比较,模型组吸气阻力(Ri)和呼气阻力(Re)升高,0.3秒用力呼气容积占用力肺活量百分比(FEV0.3/FVC)降低(P<0.01);干预组肺功能改善,与模型组比较有差异(P<0.01)。②模型组大鼠RhoA,ROCKⅡmRNA表达增高,Y-27632能够下调RhoA、ROCKⅡ的表达。③模型组Wat/Pbm、Wam/Pbm分别为(92.68±4.32)、(38.43±3.53)μm2/μm,对照组分别为(33.15±4.02)、(14.33±1.23)μm2/μm,模型组支气管壁、平滑肌层厚度增加(P<0.01);干预组Wat/Pbm、Wam/Pbm分别为(61.12±2.92)、(25.57±2.69)μm2/μm,均低于模型组大鼠(P<0.01)。结论 Y-27632通过抑制RhoA/ROCK信号通路,能够下调RhoA,ROCKⅡ的表达,抑制COPD大鼠Wat/Pbm和Wam/Pbm。Objective To observe COPD of RhoA in lung tissue of model rats,changes of ROCK Ⅱ content and investigate the effects of Y-27632 on COPD rat RhoA/Rho kinase（ROCK） pathway and its effect on airway remodeling.Methods 60 Wistar rats with the same clean grade,were randomly divided into normal control group,COPD model group,Y-27632intervention group.Each group has 20 rats.We built the COPD rat model by fumigation and Intratracheal instillation of LPS,apply intervention with ROCK specific inhibitor Y-27632,tested the pulmonary function of the rats in each group,observed the lung tissue structure under light microscope,measured the bronchial wall thickness and airway smooth muscle thickness（Wam/Pbm） by medical image analysis software（Wat/Pbm）,reflected the degree of airway remodeling.Expression of ROCK protein in lung tissue were measured by the method of determination of RhoA,ROCK Ⅱ,mRNA content in RT-PCR method.Results 1.Compared with the control group,model group inspiratory resistance（Ri） and expiratory resistance（Re） increased significantly,forced expiratory volume in 0.3 second to forced vital capacity（FEV0.3/FVC） percentage decreased significantly（P〈0.01）; the intervention group significantly improve lung function,there are significant differences compared with the model group（P〈0.01）.2.RhoA rats of model group,the expression of ROCK Ⅱ mRNA were increased,Y-27632 can down regulate the expression of RhoA,ROCK Ⅱ.3.For the Model group,Wat/Pbm,Wam/Pbm are（92.68 ± 4.32）,（38.43 ±3.53）（μm2/μm）,while those for normal control group are（33.15 ± 4.02）,（14.33 ± 1.23）（μm2/μm） in model group,the thickness of bronchial wall smooth muscle increased significantly（P〈0.01）; for intervention group,Wat/Pbm,Wam/Pbm are（61.12 ± 2.92）,（25.57 ± 2.69）（μm2/μm）,were significantly lower than that of model group rats（P〈0.01）.Conclusion Y-27632 by inhibiting the RhoA/ROCK pathway,could down regulate the expression of RhoA,ROCK Ⅱ,inhibit COP

关 键 词：RHOA ROCK信号通路 慢性阻塞性肺疾病 气道重塑 Y-27632 

分 类 号：R563.9[医药卫生—呼吸系统]