吡非尼酮与槲皮素通过S1P/SPHK信号通路抗小鼠肺纤维化比较研究

A Comparative Study of Pifenidone and Quercetin against Pulmonary Fibrosis via S1P/SPHK Signaling Pathway in Mice

目的:探讨比较吡非尼酮与槲皮素两药对肺间质纤维化的治疗作用以及与S1P/SPHK信号通路的相关性。方法:本课题组通过建立IPF动物模型,将小鼠分为模型组、对照组、吡非尼酮组、槲皮素组,对小鼠肺间质纤维化模型进行病理学观察,运用Real-time PCR检测小鼠肺组织中SphK1mRNA表达水平,Western-blot法检测小鼠肺组织中纤维化相关蛋白FN、α-SMA、CollagenⅠ、CollagenⅢ和SphK1蛋白表达水平,ELISA法检测小鼠血清和肺组织中S1P表达水平。结果:吡非尼酮与槲皮素均可以减轻博来霉素致小鼠肺纤维化损伤,有效抑制肺纤维化相关蛋白FN,α-SMA,Collagen I,的表达水平,抑制S1P、SphK1表达。结论:吡非尼酮与槲皮素均可以通过调节S1P/SphK1信号通路发挥治疗改善小鼠肺纤维化的作用,两者比较无显著性差别。

Objective:To explore the therapeutic effect of pirfenidone and quercetin on pulmonary interstitial fibrosis and their correlation with S1 P/SPHK signaling pathway.Methods:IPF mice model was established,the mice were randomly divided into the model group,the control group,the pirfenidone group and the quercetin group.Pathological changes of pulmonary interstitial fibrosis were observed in the models.Real-time PCR method was used to detect the expression level of SphK1 mRNA in lung tissues of the mice.Western blot method was used to detect related protein expressions,such as FN,α-SMA,Collagen I,CollagenⅢand SphK1 levels in lung tissue fibrosis in mice.ELISA method was used to detect the expression level of S1 P in serum and lung tissues of mice.Results:Both pirfenidone and quercetin could reduce the pulmonary fibrosis injury induced by bleomycin in mice,it could effectively inhibit the expression levels of pulmonary fibrosis-related proteins and the expressions of S1 P and SphK1.Conclusion:Both pirfenidone and quercetin can play a role in improving pulmonary fibrosis by regulating the S1 P/SphK1 signaling pathway in mice,however there is no significant difference between the two substances.