“自身清”双向调节JAK2/STATs信号通路抑制系统性红斑狼疮小鼠肺间质病变的研究  

Inhibition of Pulmonary Interstitial Lesions in Systemic Lupus Erythematosus Mice by Two-way Regulation of JAK2/STATs Signaling Pathway by"Zi Shen Qing"

作　　者：谈欣怡 谭奚扬 曹左媛 陈晓云[1] TAN Xin-yi;TAN Xi-yang;CAO Zuo-yuan;CHEN Xiao-yun(Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]上海中医药大学附属龙华医院,上海200032

出　　处：《中国中医基础医学杂志》2022年第2期213-217,共5页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金资助项目(81703998)-基于JAK/STAT3信号通路探讨滋阴清热解毒化瘀法调节不同体质狼疮小鼠Treg/Th17细胞平衡的研究;上海中医药大学“研究生创新培养”专项(Y2020033)-滋肾青芪颗粒对系统性红斑狼疮合并间质性肺病小鼠肺组织JAK/STAT通路表达的影响。

摘　　要：目的:基于酪氨酸激酶2/信号传导与转录激活子(janus kinase 2/signal transducer and activator of transcriptions,JAK2/STATs)信号通路,探索中药复方“自身清”治疗系统性红斑狼疮相关间质性肺病的作用机制。方法:40只MRL/lpr小鼠随机分为模型组、低剂量组、中剂量组、高剂量组、托法替布组,连续给药4周。苏木精-伊红染色和马松染色法观察各组小鼠肺组织炎症和纤维化程度,蛋白免疫印迹测定肺组织磷酸化STAT3(phosphorylated-STAT3,p-STAT3)、磷酸化JAK2(phosphorylated-JAK2,p-JAK2)、磷酸化STAT5(phosphorylated-STAT5,p-STAT5)、叉头状螺旋转录因3(fork-head box p3,Foxp3)、维甲酸相关核孤儿受体γt(retinoid-associated orphan receptorγt,RORγt)蛋白表达水平,ELISA测定肺组织白细胞介素17A(interleukin-17A,IL-17A)、转化生长因子β1(transforming growth factor-β1,TGF-β1)细胞因子水平。结果:与模型组比较,“自身清”中、高剂量组和托法替布组肺泡结构破坏程度及肺组织炎性细胞浸润和胶原纤维沉积程度均明显改善;“自身清”低、中、高剂量组小鼠肺组织中p-STAT3、p-JAK2、RORγt蛋白表达均显著降低(P<0.05),p-STAT5、Foxp3蛋白表达均显著升高(P<0.05);各给药组肺组织中IL-17A含量均显著降低(P<0.05),TGF-β1含量均显著升高(P<0.05)。结论:“自身清”可以选择性调控JAK2/STATs信号通路,纠正辅助性T细胞17(helper T cells17,Th17)/调节性T细胞(regulatory T cell,Treg)失衡,恢复免疫稳态,减轻肺部炎症及纤维化。Objective:To explore the mechanism of"Zi Shen Qing"on the treatment of lung inflammation and fibrosis in pulmonary interstitial lesions in systemic lupus erythematosus mice based on signaling pathways of JAK2/STATs.Methods:40 MRL/lpr mice were randomly divided into model group,low-dose group,medium-dose group,high-dose group,tofacitinib group according to body weight.After 4 weeks'intragastrical administration,HE and MASSON staining examined the pathological changes of lung tissue.The expression of phosphorylated-STAT3(p-STAT3),phosphorylated-JAK2(p-JAK2),phosphorylated-STAT5(p-STAT5),Foxp3,and RORγt protein in lung were detected by Western blot.The concentrations of IL-17A and TGF-β1 in lung were measured by Elisa.Results:Compared with the model group,the structures of lung alveolars,inflammatory cell infiltration and collagen proliferation in lung tissues in medium-dose group,high-dose group and tofacitinib groups were improved.Compared with the model group,the expressions of p-STAT3,p-JAK2,and RORγt protein in lung tissues of low-dose group,medium-dose group and high-dose group were significantly decreased(P<0.05)and the expressions of p-STAT5 and Foxp3 protein in the lung tissues of these groups were significantly increased(P<0.05).And compared with the model group,the levels of IL-17A in lung tissues of low-dose group,medium-dose group and high-dose group were significantly decreased(P<0.05),and the levels of TGF-β1 in lung tissues of these groups were significantly increased(P<0.05).Conclusion:"Zi Shen Qing"can ameliorate pulmonary inflammation and fibrosis by restoring helper T cells 17(Th17)/regulatory T cell(Treg)balance via selectively regulating JAK2/STATs signaling pathway.

关 键 词：“自身清” 系统性红斑狼疮 间质性肺病 JAK2/STATs信号通路 

分 类 号：R285.5[医药卫生—中药学]