姜黄素介导Sirt1信号通路对细菌性肺炎幼鼠免疫应答及肺间质纤维化的影响

Effects of curcumin-mediated Sirt1 signaling pathway on immune response and pulmonary fibrosis in young rats with bacterial pneumonia

目的研究姜黄素介导Sirt1信号通路对细菌性肺炎幼鼠免疫应答及肺间质纤维化的影响。方法SD雄性幼鼠90只,随机数字法将大鼠分为正常组(健康大鼠)、肺炎组(肺炎模型大鼠)、姜黄素低剂量组、姜黄素中剂量组、姜黄素高剂量组,和莫西沙星组每组15只。抗体夹心法检测免疫球蛋白水平;HE染色观察病理形态;TUNEL染色测定细胞凋亡;Masson染色观察肺纤维化情况;Western blot检测Sirt1、NF-κB蛋白表达水平。结果肺炎组幼鼠肺泡结构破坏,有炎性细胞浸润;姜黄素低剂量组与肺炎组相比无明显改善;中、高剂量组与莫西沙星组较肺炎组有所改善且以姜黄素高剂量组效果最明显。肺炎组肺组织中肺泡结构破坏,形成大量纤维化;姜黄素低剂量组与肺炎组相比无明显改善;中、高剂量组与莫西沙星组较肺炎组有所改善且以姜黄素高剂量组效果最佳。与正常组相比,肺炎组IgG、IgM、IgA、CD4+、Sirt1表达降低,CD8^(+)、NF-κB、NF-κB p65升高(P<0.05)。在经过姜黄素干预后IgG、IgM、IgA、CD4^(+)、Sirt1表达升高,CD8^(+)、NF-κB、NF-κB p65表达降低(P<0.05),且呈现出明显的剂量依赖性。结论姜黄素可能通过调控Sirt1通路,提高肺炎链球菌幼鼠免疫功能,改善肺纤维化程度,对肺组织起保护作用。

This study was performed to investigate the effect of curcumin-mediated Sirt1 signaling pathway on the immune responses and pulmonary fibrosis in young rats with bacterial pneumonia.Total of 90 male SD rats were recruited as randomly divided into normal group(healthy rats),pneumonia group(pneumonia model rats),low-dose curcumin group,middle-dose curcumin group,and high-dose curcumin group,moxifloxacin group,with 15 animals in each group.ELISA was used to detect the levels of immunoglobulins;HE staining was used to observe the pathological morphology;TUNEL staining was used to determine cell apoptosis;Masson staining was used to observe pulmonary fibrosis;and Western blot was used to detect of the expression levels of Sirt1,NF-κB proteins.Data showed that alveolar structure was destroyed and inflammatory cells were infiltrated in the pneumonia group;curcumin low-dose group demonstrated no significant difference to pneumonia group,while medium/high dose of curcumin and moxifloxacin,especially high dose curcumin,could alleviate these pathological changes in pneumonia rats.Compared with the normal group,the expression of IgG,IgM,IgA,CD3^(+),CD4^(+),Sirt1 in the pneumonia group decreased,and the expression of CD8^(+),NF-κB,and NF-κB p65 increased(P<0.05).After the intervention of curcumin,the expression of IgG,IgM,IgA,CD3^(+),CD4^(+),Sirt1 increased,and the expression of CD8^(+),NF-κB,NF-κB p65 decreased(P<0.05).Taken together,curcumin may improve the immune function of S.pneumoniae-infected young rats,alleviate the degree of pulmonary fibrosis,and protect lung tissue by regulating the Sirt1 pathway.