TSLP siRNA干预对哮喘模型大鼠气道重塑的作用及对ERK信号通路的影响

Effect of TSLP siRNA intervention on airway remodeling and ERK signaling pathway in asthmatic model rats

目的分析胸腺基质淋巴细胞生成素(TSLP)小干扰RNA(siRNA)干预对哮喘模型大鼠气道重塑的作用及对细胞外信号调节激酶(ERK)信号通路的影响。方法选取清洁及健康的雄性大鼠56只,随机选取14只为正常组,剩余42只建立哮喘模型,分为模型组、空白对照组和TSLP siRNA干预组,各14只。Image-Pro Plus软件计算出大鼠的小气道支气管壁总管壁面积、小气道支气管壁内管壁面积和支气管壁平滑肌的面积,生理记录仪记录大鼠的肺顺应性和肺弹性阻力,显微镜下观察大鼠白细胞数量、嗜酸性粒细胞(EOS)数量,并计算出EOS/白细胞的值,Western blot法检测细胞外信号调节激酶-1(ERK1)、伤害性信息与即刻早期基因(C-FOS)、血小板衍生因子(PDGF)蛋白水平表达。结果与模型组、空白对照组相比,TSLP siRNA干预组小气道支气管壁总管壁面积、小气道支气管壁内壁面积、支气管壁平滑肌面积均减小,差异有统计学意义(P<0.05);与模型组、空白对照组相比,TSLP siRNA干预组肺顺应性均升高,肺弹性阻力均降低,差异有统计学意义(P<0.05);与模型组、空白对照组相比,TSLP siRNA干预组白细胞、EOS/白细胞均降低,差异有统计学意义(P<0.05);与模型组、空白对照组相比,TSLP siRNA干预组ERK1、C-FOS、PDGF通路蛋白均降低,差异有统计学意义(P<0.05)。结论TSLP siRNA干预通过调控ERK信号通路相关蛋白,改善气道重塑指标,提高大鼠的肺顺应性,降低大鼠的肺弹性阻力,抑制炎性反应。

Objective To analyze the effects of thymic stromal lymphopoietic hormone(TSLP)small interfering RNA(siRNA)intervention on the airway remodeling in asthmatic model rats and its effects on extracellular signalling regulated kinase(ERK)signaling pathway.Methods Fifty-six clean and healthy male rats were selected.Fourteen cases were randomly selected as the normal group.The remaining 42 cases were built the asthmatic models and divided into the model group,blank control group and TSLP siRNA intervention group,14 cases in each group.The Image-Pro Plus software was used to calculate the rat small airway wall total area of bronchial wall,small airway smooth muscle of the bronchial wall inside tube wall area and the bronchial wall area.The rat lung compliance and pulmonary elastic resistance were recorded by the physiological recorder.The white blood cells count and eosinophils(EOS)count were observed by microscope,and the ratio of EOS/white blood cells was calculated.Western blot was used to detect the extracellular signal regulated kinase-1(ERK1),harmful information,the proteins of immediate early gene(C-FOS)and platelet-derived factor(PDGF)protein levels.Results Compared with the model group and blank control group,the total bronchial wall area,inner wall area and smooth muscle area of the bronchial wall of the small airway in the TSLP siRNA intervention group were all reduced,and the difference was statistically significant(P<0.05).Compared with the model group and blank control group,the lung compliance in the TSLP siRNA intervention group was increased and the lung elastic resistance was decreased,showing statistical differences(P<0.05).Compared with the model group and blank control group,the white blood cells and EOS/white blood cells in the TSLP siRNA intervention group were all decreased,with statistically significant differences(P<0.05).Compared with the model group and blank control group,the levels of ERK1,C-FOS,PDGF pathway proteins in the TSLP siRNA intervention group were all decreased,with statistically significant differences(P<0.05).Conclusion TSLP siRNA intervention can improve airway remodeling indexes by regulating the ERK signaling pathway related proteins,improve the rat lung compliance,reduce the pulmonary elastic resistance and inhibit the inflammatory response.