促愈熏洗方通过SOCS1介导JAK/STAT通路调控巨噬细胞M2型极化的机制研究  

Mechanism of Cuyu Xunxi formula regulating M2-type polarization of macrophages by SOCS1 mediating JAK/STAT pathways

作　　者：瞿胤 陆宏[1] 方臣阳 韩晔[1] 杨巍[1] 郑德[1] QU Yin;LU Hong;FANG Chenyang;HAN Ye;YANG Wei;ZHENG De(Department of Proctology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201202,China)

机构地区：[1]上海中医药大学附属曙光医院肛肠科,上海201202

出　　处：《陕西中医》2024年第12期1587-1591,1597,共6页Shaanxi Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金青年基金资助项目(82104868);国家中医药管理局第七批全国老中医药专家学术经验继承工作项目[国中医药人教函(2022)76号];上海市科研计划项目(21Y11923200);上海市卫生健康委员会科研项目(202340278);上海中医药大学附属医院“临床研究型骨干人才培养计划”项目(2023LCRC07)。

摘　　要：目的:探究促愈熏洗方通过细胞因子信号转导抑制蛋白1(SOCS1)介导Janus激酶/信号转导和转录激活因子(JAK/STAT)通路调控巨噬细胞M2型极化的作用机制。方法:用白细胞介素-4(IL-4)刺激巨噬细胞系RAW264.7,诱导巨噬细胞M2极化,RT-qPCR与Western blot检测SOCS1、SOCS2和SOCS3表达,筛选效应因子。脂多糖(LPS)诱导巨噬细胞M1极化,分别用促愈熏洗方、siSOCSs处理细胞,检测M2型巨噬细胞表面标记分子(CD206、CD163)、相关炎症因子[IL-10、IL-13和转化生长因子β(TGF-β)]及JAK/STAT信号通路(STAT3、STAT6)表达。结果:与对照组比较,IL-4组细胞中SOCS1 mRNA及蛋白表达升高,SOCS3 mRNA及蛋白表达降低(均P<0.05),其中SOCS1表达变化最为显著。与对照组比较,IL-4组p-STAT3、p-STAT6、CD206和CD163蛋白表达及IL-10、IL-13、TGF-β含量升高(均P<0.05);与IL-4组比较,IL-4+siSOCS1组p-STAT3、p-STAT6、CD206、CD163及IL-10、IL-13、TGF-β降低(均P<0.05)。与对照组比较,LPS组CD206、CD163、IL-10、IL-13、TGF-β、p-STAT3、p-STAT6降低(均P<0.05);与LPS组比较,LPS+促愈熏洗方组SOCS1、CD206、CD163、IL-10、IL-13、TGF-β、p-STAT3、p-STAT6升高(均P<0.05);与LPS+促愈熏洗方组比较,LPS+促愈熏洗方+siSOCS1组SOCS1、CD206、CD163、IL-10、IL-13、TGF-β、p-STAT3、p-STAT6降低(均P<0.05)。结论:促愈熏洗方通过SOCS1激活JAK/STAT通路诱导巨噬细胞M2型极化。Objective:To explore the mechanism of Cuyu Xunxi formula regulating M2-type polarization of macrophages by suppressor of cytokine signaling 1(SOCS1)mediating Janus kinase/signal transduction and activator of transcription(JAK/STAT)pathways.Methods:Macrophage line RAW264.7 was stimulated with interleukin-4(IL-4)to induce M2 polarization of macrophages.The expressions of SOCS1,SOCS2 and SOCS3 were detected by RT-qPCR and Western blot to screen effecting factors.M1 polarization of macrophages was induced by lipopolysaccharide(LPS),and cells were treated with Cuyu Xunxi formula and siSOCSs.The expressions of marker molecules(CD206,CD163)on M2-type macrophages surface,related inflammatory factors(IL-10,IL-13,TGF-β)and JAK/STAT signaling pathways(STAT3,STAT6)were detected.Results:Compared with control group,expressions of SOCS1 mRNA and protein were increased,while expressions of SOCS3 mRNA and protein were decreased in IL-4 group(all P<0.05),and the changes of SOCS1 expression were the most significant.Compared with control group,expressions of p-STAT3,p-STAT6,CD206 and CD163 proteins,and levels of IL-10,IL-13 and TGF-βwere increased in IL-4 group(all P<0.05).Compared with IL-4 group,expressions of p-STAT3,p-STAT6,CD206 and CD163 proteins,and levels of IL-10,IL-13 and TGF-βwere decreased in IL-4+siSOCS1 group(all P<0.05).Compared with control group,CD206,CD163,IL-10,IL-13,TGF-β,p-STAT3 and p-STAT6 were decreased in LPS group(all P<0.05).Compared with LPS group,SOCS1,CD206,CD163,IL-10,IL-13,TGF-β,p-STAT3 and p-STAT6 were increased in LPS+Cuyu Xunxi formula group(all P<0.05).Compared with LPS+Cuyu Xunxi formula group,SOCS1,CD206,CD163,IL-10,IL-13,TGF-β,p-STAT3 and p-STAT6 were decreased in LPS+Cuyu Xunxi formula+siSOCS1 group(all P<0.05).Conclusion:Cuyu Xunxi formula can induce M2-type polarization of macrophages by SOCS1 activating JAK/STAT pathways.

关 键 词：促愈熏洗方 创面修复 巨噬细胞极化 M1/M2表型 细胞因子信号转导抑制蛋白1 Janus激酶/信号转导和转录激活因子信号通路 

分 类 号：R285.5[医药卫生—中药学]