辛伐他汀对烟雾暴露大鼠肺血管Toll样受体4表达及肺血管重塑的影响

Effects of simvastatin on Toll-like receptor 4 expression and pulmonary vascular remodeling in smoke-exposed rats

目的探讨辛伐他汀对烟雾暴露大鼠肺血管Toll样受体4(TLR4)表达及肺血管重塑的影响。方法将30只清洁级雄性健康SD大鼠随机分为正常对照组、烟雾暴露组及辛伐他汀干预组,每组各10只。正常对照组大鼠吸入新鲜空气,常规食物喂养。烟雾暴露组及辛伐他汀干预组大鼠均接受8周的烟雾暴露,辛伐他汀干预组大鼠在暴露时间内行辛伐他汀鼻饲灌胃。造模结束后取3组大鼠的肺动脉和左主支气管标本,采用苏木素-伊红(HE)染色法观察肺血管形态学变化,并测量各组大鼠肺血管管壁面积/血管总面积(WA%)、血管壁厚度/血管外径(WT%)。采用免疫组织化学染色法检测肺血管TLR4蛋白表达水平。采用逆转录聚合酶链反应(RT-PCR)检测肺血管TLR4 mRNA的表达水平。采用Pearson法分析TLR4与肺血管重塑的相关性。结果烟雾暴露组和辛伐他汀组大鼠WA%、WT%、肺动脉TLR4蛋白及TLR4 mRNA表达水平明显高于正常对照组,辛伐他汀组大鼠WA%、WT%、TLR4蛋白及TLR4 mRNA表达水平明显低于烟雾暴露组(P<0.05)。Pearson相关分析结果显示,TLR4 mRNA与WA%、WT%均呈正相关(P<0.05)。结论烟雾暴露可上调大鼠肺血管TLR4蛋白的表达水平,诱导肺血管重塑;而辛伐他汀药物干预能够降低其TLR4 mRNA的表达水平,逆转肺血管重塑。

Objective To investigate the effect of simvastatin on the expression of Toll-like receptor 4(TLR4)and pulmonary vascular remodeling in smoke exposure rats.Methods Thirty clean grade male healthy SD rats were randomly divided into normal control group,smoke exposure group and simvastatin intervention group,with 10 rats in each group.Rats in the normal control group inhaled fresh air and were fed with conventional food.Rats in smoke exposure group and simvastatin intervention group were exposed to smoke for 8 weeks.At the end of modeling,the pulmonary artery and left main bronchus specimens of the 3 groups were taken to observe the morphological changes of pulmonary vessels by hematoxylin-eosin(HE)staining method,and the pulmonary vascular wall area/total vascular area(WA%)and vascular wall thickness/vascular diameter(WT%)were measured.The expression of TLR4 protein in pulmonary vessels was detected by immunohistochemistry.The expression of TLR4 mRNA was detected by reverse transcription polymerase chain reaction(RT-PCR).Pearson method was used to analyze the correlation between TLR4 and pulmonary vascular remodeling.Results WA%,WT%and the expression levels of TLR4 protein and TLR4 mRNA in pulmonary artery in smoke exposure group and simvastatin group were significantly higher than those in normal control group,and WA%,WT%and the expression of TLR4 protein and TLR4 mRNA in simvastatin group were significantly lower than those in smoke exposure group(P<0.05).Pearson correlation analysis showed that TLR4 mRNA was positively correlated with WA%and WT%(P<0.05).Conclusion Smoke exposure can upregulate the expression level of TLR4 protein and induce pulmonary vascular remodeling.Simvastatin can reduce its expression level of TLR4 mRNA and reverse pulmonary vascular remodeling.