桔梗皂苷E通过抑制JAK/STAT信号阻抑巨噬细胞M2极化改善肺纤维化的机制  

Mechanism of pulmonary platycoside E ameliorates fibrosis by inhibiting JAK/STAT signaling to inhibit macrophage M2 polarization

作　　者：刘芸芸 李雅茹 李霄 金宁一 李一权 朱光泽[3] LIU Yunyun;LI Yaru;LI Xiao;JIN Ningyi;LI Yiquan;ZHU Guangze(College of Integrated Traditional Chinese and Western Medicine,Changchun University of Traditional Chinese Medicine,Changchun 130117,China;Changchun Veterinary Research Institute,Chinese Academy of Agriculture Sciences,Changchun 130122,China;Department of Clinical Laboratory,Changchun University of Chinese Medicine Affiliated Hospital of Jilin Province Hospital,Changchun 130021,China)

机构地区：[1]长春中医药大学中西医结合学院,长春130117 [2]中国农业科学院长春兽医研究所,长春130122 [3]长春中医药大学附属医院检验科,长春130021

出　　处：《中国免疫学杂志》2025年第4期803-807,共5页Chinese Journal of Immunology

基　　金：吉林省自然科学基金项目(YDZJ202201ZYTS257);吉林省教育厅优秀青年科技项目(JJKH20241039KJ)。

摘　　要：目的:从抑制JAK/STAT信号阻抑巨噬细胞M2极化途径阐述桔梗皂苷E(PE)对博来霉素(BLM)诱导的肺纤维化模型小鼠的干预作用及其机制。方法:通过随机抽样将40只BALB/c小鼠划分为5组:空白对照组、模型组、吡非尼酮(PDF)实验组、PE高剂量组、PE低剂量组,每组8只。适应性饲养后,除空白对照组外,实验组小鼠采用BLM鼻滴法诱导肺纤维化小鼠模型。采用HE和Masson染色研究小鼠肺部组织的病理性变化;ELISA检测小鼠血清中IL-10、IL-4、IL-17A、TNF-α浓度;采用免疫荧光技术检测肺组织中CD206、CD11b表达;Western blot检测肺组织中JAK1、p-JAK1、STAT6、p-STAT6蛋白表达。结果:与空白组相比,模型组小鼠组织结构扭曲,肺泡壁变厚,形成纤维化灶,其肺泡炎性分数和胶原体积分数显著升高(P<0.01)。ELISA结果表明,与模型组相比,小鼠血清IL-4、IL-6、IL-10、TNF-α浓度有所降低;免疫荧光技术检测结果表明,经PE处理的CD11b和CD206荧光强度均明显降低。Western blot结果表明,模型小鼠肺部组织中JAK1、p-JAK、STAT6、p-STAT6蛋白表达显著升高,而经PE处理后,以上蛋白表达水平均降低。结论:PE能有效改善BLM引起的小鼠肺纤维化,其机制可能与抑制JAK/STAT通路阻抑巨噬细胞M2极化有关。Objective:To investigate the role of Platycoside E(PE)in a mouse model of bleomycin(BLM)-induced pulmonary fibrosis by targeting the JAK/STAT signaling pathway to suppress macrophage M2 polarization.Methods:Forty BALB/c mice were randomly assigned to five experimental groups:blank control group,model group,pirfenidone(PDF)experimental group,PE high-dose group and PE low-dose experimental group,each with eight mice.After adaptive feeding,except for blank control group,all mice were used in the model of BLM nasal drip-induced pulmonary fibrosis.HE and Masson staining were employed to examine pathological alterations of lung tissue in mice;ELISA to detect concentrations of IL-10,IL-4,IL-17A and TNF-αin mice serum;expressions of CD206 and CD11b in lung tissue were detected by immunofluorescence.Western blot to detect protein expressions of JAK1,p-JAK1,STAT6 and p-STAT6 in lung tissues.Results:Compared with blank control group,tissues in model group showed distorted structure and thickened alveolar walls,fibrotic foci were formed,and alveolar inflammatory fraction and collagen volume fraction were significantly increased(P<0.01).ELISA showed that concentrations of IL-4,IL-10,IL-6 and TNF-αin serum were significantly reduced compared to those of model group.Immunofluorescence showed that fluorescence intensity of CD11b and CD206 treated by PE were decreased significantly.Western blot showed that expressions of JAK1,p-JAK,STAT6 and p-STAT6 proteins were significantly elevated in lung tissues of model mice.Following PE treatment,levels of the above proteins were diminished.Conclusion:PE can effectively improve lung fibrosis induced by BLM in mice,the mechanism may be related to the inhibition of JAK/STAT pathway to block macrophage M2 polarization.

关 键 词：肺纤维化 巨噬细胞 桔梗皂苷E 炎症 

分 类 号：R256.1[医药卫生—中医内科学]