黄芪甲苷Ⅳ通过抑制TIM-1信号通路增加Th1/Th2细胞比率减轻IgA肾病小鼠肾损伤  

Astragaloside Ⅳ reduces renal injury in mice with IgA nephropathy by inhibiting TIM-1 signaling pathway and increasing Th1/Th2 cell ratio

作　　者：王晓亮 谭鹏 孔维信[1] WANG Xiaoliang;TAN Peng;KONG Weixin(Department of Nephrology,Suzhou Jiulong Hospital,School of Medicine,Shanghai Jiao Tong University,Suzhou 215000,China)

机构地区：[1]上海交通大学医学院苏州九龙医院肾内科,江苏苏州215000

出　　处：《细胞与分子免疫学杂志》2024年第6期501-507,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：2018年苏州市民生科技-医疗卫生应用基础研究(SYS2018007)。

摘　　要：目的探讨黄芪甲苷Ⅳ(AS-Ⅳ)对IgA肾病(IgAN)小鼠1型辅助T(Th1)细胞/Th2细胞平衡的影响及其可能作用机制。方法建立BALB/c小鼠IgAN模型,造模成功小鼠随机分为模型组、AS-Ⅳ低、中和高剂量组各10只,另设对照组10只。AS-Ⅳ低、中和高剂量组小鼠灌胃(12.5、25、50)mg/kg AS-Ⅳ混悬液(生理盐水配制),对照组及模型组给予等量生理盐水。测定各组小鼠24 h尿蛋白(24 hUPr)含量和尿红细胞计数;测定小鼠血尿素氮(BUN)、血清肌酐(Scr)和白蛋白(ALB)水平;ELISA检测各组小鼠血清γ干扰素(IFN-γ)、白细胞介素4(IL-4)和IL-10水平;流式细胞术检测小鼠外周血Th1/Th2细胞比率;HE染色观察小鼠肾组织病理学变化;反转录PCR和Western blot法分别检测小鼠肾组织中T细胞免疫球蛋白和黏蛋白结构域1(TIM-1)、Toll样受体4(TLR4)的mRNA和蛋白表达。结果与模型组比较,AS-Ⅳ低、中和高剂量组小鼠第12周和第15周尿红细胞计数、24 h UPr、BUN、Scr、IL-4、IL-10水平、Th2细胞比例、TIM-1与TLR4 mRNA和蛋白表达水平均明显降低,ALB、IFN-γ水平、Th1细胞比例和Th1/Th2细胞比率升高,且以AS-Ⅳ高剂量组效果最佳。结论AS-Ⅳ通过抑制TIM-1信号通路,增加Th1/Th2细胞比率,抑制炎症反应,减轻IgAN小鼠肾损伤。Objective To investigate the effects of astragalosideⅣ(AS-Ⅳ)on the balance of T helper type 1(Th1)and Th2 cells in mice with IgA nephropathy(IgAN)and its possible mechanism.Methods The IgAN model of BALB/c mice was established.Successfully modeled mice were randomly divided into four groups:model,AS-Ⅳlow dose,AS-Ⅳmedium dose and AS-Ⅳhigh dose groups,with 10 mice in each group.Another 10 mice served as the control group.Mice in the low,medium and high dose groups were administered 12.5,25 and 50 mg/kg AS-Ⅳsuspension(prepared in normal saline)by gavage,while the control and model groups were given an equivalent volume of normal saline.The 24-hour urinary protein(24 h UPr)content and urine red blood cell count were measured in each group.The levels of blood urea nitrogen(BUN),serum creatinine(Scr)and albumin(ALB)were determined.Serum interferonγ(IFN-γ),interleukin 4(IL-4)and IL-10 levels were detected by ELISA.The ratio of Th1/Th2 cells in peripheral blood of mice was detected using flow cytometry.Histopathological changes in the kidney of mice were observed by HE staining.RT-PCR and Western blot were used to detect the mRNA and protein expressions of T cell immunoglobulin and mucin domain gene 1(TIM-1),Toll-like receptor 4(TLR4)in mouse kidney tissue.Results Compared with the model group,in weeks 12 and 15,the urine red blood cell count,24 h UPr,BUN,Scr,levels of IL-4 and IL-10,the proportion of Th2 cells,as well as the mRNA and protein expression levels of TIM-1 and TLR4 were significantly decreased in the low,medium and high dose groups of AS-Ⅳ,and the levels of ALB,IFN-γ,the proportion of Th1 cells and Th1/Th2 cell ratio were increased,with the high-dose group showing the best effects.Conclusion AS-Ⅳcan inhibit TIM-1 signaling pathway,increase the Th1/Th2 cell ratio,inhibit the inflammatory reaction,and alleviate the renal injury in IgAN mice.

关 键 词：黄芪甲苷(AS-Ⅳ) IgA肾病(IgAN) TH1/TH2细胞平衡 T细胞免疫球蛋白和黏蛋白结构域1(TIM-1) Toll样受体4(TLR4) 

分 类 号：R285.5[医药卫生—中药学] R692[医药卫生—中医学] R392.5R364.5