消栓通脉汤调控JAK2/STAT3影响树突状细胞功能治疗深静脉血栓形成  

Xiaoshuantongmai Decoction regulates JAK2/STAT3 to affect the function of dendritic cells in treatment of deep vein thrombosis

作　　者：张云虹 艾爽[2] 褚楚 王雨柔 张亭亭 祖会艳 范楠楠 王彬[3] 李霞[1] ZHANG Yunhong;AI Shuang;CHU Chu;WANG Yurou;ZHANG Tingting;ZU Huiyan;FAN Nannan;WANG Bin;LI Xia(Innovative Institute of Chinese Medicine and Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;The Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250012,China;The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250001,China)

机构地区：[1]山东中医药大学中医药创新研究院,济南250355 [2]山东中医药大学附属医院,济南250012 [3]山东中医药大学第二附属医院,济南250001

出　　处：《中国免疫学杂志》2025年第4期769-774,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金面上项目(81673981);国家中医药管理局科技司共建科技项目(GZY-KJS-SD-2023-034,GZY-KJS-SD-2023-046);山东省自然科学基金重大基础研究项目(ZR2023ZD56);山东省自然科学基金联合基金项目(ZR2022LZY011);山东省中央引导地方科技发展资金项目(YDZX20203700001407);国家中医药管理局青年岐黄学者项目;泰山学者特聘专家项目(tstp20240513);山东省中医药高层次人才培育项目(领军人物)。

摘　　要：目的:探讨消栓通脉汤(XSTMD)调控JAK2/STAT3信号通路影响树突状细胞(DCs)功能治疗深静脉血栓形成(DVT)的分子机制。方法:XSTMD治疗DVT后,ELISA检测DVT患者血浆中纤维蛋白原(FGB)及D-二聚体(D2D)蛋白表达,流式细胞术检测DVT患者外周血单个核细胞(PBMCs)中pDC、cDC亚群比例及HLA-DR蛋白表达,qRT-PCR检测CD80、CD86 mRNA水平,Western blot检测DVT患者、小鼠PBMC中JAK2、STAT3蛋白及磷酸化(p-JAK2、p-STAT3)水平。XSTMD含药血清处理LPS诱导的小鼠DC2.4细胞,Western blot检测JAK2、STAT3、p-JAK2、p-STAT3蛋白水平,ELISA检测细胞培养上清中IL-6、TNF-α、IL-10及TGF-β1蛋白水平。结果:XSTMD治疗后,DVT小鼠血栓重量及长度明显减小(P<0.001)。与治疗前相比,XSTMD临床治疗后,DVT患者血浆中FGB及D2D表达显著降低(P<0.001),外周血pDC比例显著升高,cDC比例显著降低(P<0.01),HLA-DR蛋白表达及CD80、CD86 mRNA水平显著降低(P<0.05,P<0.01,P<0.001)。XSTMD作用后,DVT患者及小鼠PBMC中p-JAK2、p-STAT3蛋白水平均显著升高(P<0.05)。XSTMD含药血清处理LPS诱导的DC2.4细胞后,p-JAK2、p-STAT3蛋白水平均显著升高(P<0.05),细胞上清中IL-6、TNF-α蛋白表达显著降低,IL-10、TGF-β1蛋白表达显著升高(P<0.01,P<0.001)。结论:XSTMD通过调控JAK2/STAT3信号通路促进DCs向pDC分化,减轻炎症损伤,进而治疗DVT。Objective:To investigate the molecular mechanism of Xiaoshuantongmai Decoction(XSTMD)targeting JAK2/STAT3 signaling pathway to regulate the function of dendritic cells(DCs)in treatment of deep vein thrombosis(DVT).Methods:After treatment of DVT with XSTMD,expressions of fibrinogen beta chain(FGB)and D-dimer(D2D)protein in plasma of patients with DVT were detected by ELISA,proportion of plasmacytoid dendritic cell(pDC)and conventional dendritic cell(cDC),and expression of HLA-DR protein in peripheral blood mononuclear cells(PBMCs)of patients with DVT were detected by flow cytometry,expressions of CD80 and CD86 mRNA were detected by qRT-PCR,Western blot was used to detect protein levels of JAK2,STAT3 and phosphorylation(p-JAK2 and p-STAT3)in PBMC of DVT patients and mice.LPS-induced mouse DC2.4 cells were treated with XSTMD drugcontaining serum.Western blot was used to determine the protein levels of JAK2,STAT3,p-JAK2 and p-STAT3.ELISA was used to detect protein levels of IL-6,TNF-α,IL-10 and TGF-β1 in cell culture supernatant.Results:After treatment with XSTMD,weight and length of thrombus were significantly reduced in mice with DVT(P<0.001).Compared with before treatment,expressions of FGB and D2D were significantly decreased in plasma of DVT patients(P<0.001),proportion of pDC was significantly increased,while proportion of cDC was significantly decreased in PBMC of DVT patients(P<0.01),expression of HLA-DR protein and mRNA levels of CD80 and CD86 were significantly decreased in PBMC of DVT patients(P<0.05,P<0.01,P<0.001)after treatment with XSTMD.Levels of p-JAK2 and p-STAT3 protein were significantly increased in PBMC from DVT patients and mice treated with XSTMD(P<0.05).After treatment with serum containing XSTMD,protein levels of p-JAK2 and p-STAT3 induced by LPS were significantly increased in murine DC2.4 cells(P<0.05).Protein expressions of IL-6 and TNF-αwere significantly decreased,while protein expressions of IL-10 and TGF-β1 were significantly increased in cell supernatant(P<0.01,P<0.001).Conclusio

关 键 词：深静脉血栓形成 消栓通脉汤 JAK2/STAT3 树突状细胞 炎症损伤 

分 类 号：R285.5[医药卫生—中药学]