BMSCs调节TGF-β1/Smad通路对肝硬化大鼠免疫调节功能的作用研究  

Study on effects of BMSCs regulating TGF-β1/Smad pathway on immune regulation in rats with liver cirrhosis

作　　者：卢斯霞 胡旭东 高欣 程聪 陈思 LU Sixia;HU Xudong;GAO Xin;CHENG Cong;CHEN Si(Department of Hepatology,Wuhan Jinyintan Hospital,Tongji Medical College of Huazhong University of Science and Technology,Hubei Clinical Research Center for Infectious Diseases,Wuhan Research Center for Communicable Disease Diagnosis and Treatment,Chinese Academy of Medical Sciences,Joint Laboratory of Infectious Diseases and Health,Wuhan Institute of Virology and Wuhan Jinyintan Hospital,Chinese Academy of Sciences,Wuhan 430010,China)

机构地区：[1]华中科技大学同济医学院附属武汉金银潭医院肝病科湖北省传染病临床医学研究中心中国医学科学院武汉传染性疾病诊治研究中心中国科学院武汉病毒研究所&武汉市金银潭医院感染性疾病与健康联合实验室,武汉430010

出　　处：《中国免疫学杂志》2022年第10期1183-1188,共6页Chinese Journal of Immunology

摘　　要：目的:探究BMSCs调节TGF-β1/Smad通路对肝硬化大鼠免疫调节功能的作用。方法:36只大鼠随机分为对照组、模型组和BMSCs组,每组12只。模型组和BMSCs组大鼠通过四氯化碳构建肝纤维化模型,BMSCs组大鼠尾静脉注射BMSCs(3×10^(6)个)。检测各组大鼠肝功能指标,HE和Masson染色检测肝组织损伤和纤维化情况,流式细胞术检测外周血中Th17细胞和Treg比例。Western blot、RT-qPCR检测胶原蛋白(Col)Ⅰ、ColⅢ、TGF-β1和Smad水平。结果:模型组大鼠ALT、AST、纤维化水平、肝组织ColⅠ、ColⅢ、TGF-β1和Smad mRNA和蛋白水平显著高于对照组(P<0.05)。BMSCs组ALT、AST、纤维化水平、肝组织ColⅠ、ColⅢ、TGF-β1和Smad mRNA和蛋白水平显著低于模型组(P<0.05)。模型组大鼠Th17细胞占比和Th17/Treg显著高于对照组,Treg水平显著低于对照组(P<0.05)。BMSCs组Th17水平和Th17/Treg显著低于模型组,Treg水平显著高于模型组(P<0.05)。模型组淋巴细胞TGF-β1和Smad蛋白水平高于对照组(P<0.05),BMSCs组TGF-β1和Smad蛋白水平显著低于模型组(P<0.05)。结论:BMSCs可能通过抑制TGF-β1/Smad通路减少肝组织中Col表达,并诱导失衡的Th17/Treg向Treg偏移,从而缓解肝纤维化。Objective:To explore effects of BMSCs regulating TGF-β1/Smad pathway on immunoregulatory function of liver cirrhotic rats.Methods:Thirty-six rats were randomly divided into control group,model group and BMSCs group,with 12 rats in each group.Rats in model group and BMSCs group were constructed liver fibrosis models via carbon tetrachlorid.Rats in BMSCs group were injected with BMSCs(3×10~6 cells)through tail vein.Liver function indexes of each group were detected,and liver tissue damage and fibrosis were detected by HE and Masson staining.Ratios of Th17 cells and Treg in peripheral blood was detected by flow cytometry.Levels of collagen(Col)Ⅰ and Col Ⅲ,TGF-β1 and Smad were detected by Western blot and RT-qPCR.Results:ALT,AST,fibrosis level,Col Ⅰ,Col Ⅲ,TGF-β1 and Smad mRNA and protein levels in model group were significantly higher than those in control group(P<0.05).ALT,AST,fibrosis level,Col Ⅰ,Col Ⅲ,TGF-β1 and Smad mRNA and protein levels in BMSCs group were significantly lower than those in model group(P<0.05).Th17 percentage and Th17/Treg of model group were significantly higher than those in control group,and Treg level was significantly lower than that in control group(P<0.05).Th17 level and Th17/Treg in BMSCs group were significantly lower than those in model group,and Treg level was significantly higher than that in model group(P<0.05).TGF-β1and Smad protein levels of lymphocytes in model group were higher than those in control group(P<0.05).TGF-β1 and Smad protein levels in BMSCs group were significantly lower than those in model group(P<0.05).Conclusion:BMSCs may reduce expression of Col in liver tissue by inhibiting TGF-β1/Smad pathway,and induce imbalance of Th17/Treg balance to shift to Treg,thereby alleviating liver fibrosis.

关 键 词：肝纤维化 BMSCS 调节性T细胞 T辅助细胞17 TGF-β1/Smad通路 

分 类 号：R392[医药卫生—免疫学]