摘要
目的:初步探讨高良姜素(Gal)调节基质细胞衍生因子1(SDF-1)/CXC趋化因子受体4(CXCR4)信号通路对肾病综合征(NS)大鼠免疫功能的影响。方法:尾静脉注射阿霉素建立NS大鼠模型,造模成功后,随机分为Model组、Gal低、中、高剂量组、激活剂组,随机选取12只大鼠作为control组,各组灌胃并腹腔注射相应药物,1次/d,连续6周,检测大鼠24 h尿蛋白和尿素氮(BUN)、肌酐(Scr)、总胆固醇(TC)等生化指标;HE染色观察大鼠肾组织病理损伤;取脾脏、胸腺并称重,计算器官指数;流式细胞仪检测大鼠外周血中CD3^(+)T、CD4^(+)T、CD8^(+)T、Th1、Th2细胞水平;ELISA检测大鼠血清中IL-10、IL-2、TNF-α、IgG、IgM;qRT-PCR和Western blot检测SDF-1、CXCR4 mRNA及蛋白表达。结果:与control组比较,Model组大鼠24 h尿蛋白、BUN、Scr、TC、甘油三酯(TG)含量、CD8^(+)T、Th1、Th1/Th2、IL-2、TNF-α、SDF-1、CXCR4 mRNA及蛋白表达均显著升高,白蛋白(ALB)含量、脾脏指数、胸腺指数、CD3^(+)T、CD4^(+)T、Th2细胞比例及CD4^(+)T/CD8^(+)T、IL-10、IgG、IgM水平均显著降低(P<0.05);与Model组比较,Gal低、中、高剂量组大鼠24 h尿蛋白、BUN、Scr、TC、TG含量、CD8^(+)T、Th1、Th1/Th2、IL-2、TNF-α、SDF-1、CXCR4 mRNA及蛋白表达逐渐降低,ALB含量、脾脏指数、胸腺指数、CD3^(+)T、CD4^(+)T、Th2细胞比例及CD4^(+)T/CD8^(+)T、IL-10、IgG、IgM水平逐渐升高(P<0.05);与Gal高剂量组相比,激活剂组大鼠上述指标变化均显著逆转(P<0.05)。结论:Gal可能通过抑制SDF-1/CXCR4通路增强T淋巴细胞免疫功能,从而减轻NS大鼠肾损伤。
Objective:To investigate effect of galangin(Gal)on immune function in nephrotic syndrome(NS)rats by regulating stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor 4(CXCR4)signaling pathway.Methods:A NS rat model was established by injecting doxorubicin into tail vein.After successful modeling,rats were randomly grouped into Model group,Gal low,medium and high doses groups,activator group.Twelve rats were randomly selected as control group,and each group was given corre-sponding drug by gavage and intraperitoneal injection,once a day for 6 consecutive weeks.Biochemical indicators such as 24-hour urine protein,urea nitrogen(BUN),creatinine(Scr)and total cholesterol(TC)were detected in rats;HE staining was applied to observe pathological damage in rat kidney tissue;spleen and thymus were taken and weighed,and organ index was calculated;flow cytometry was applied to detect levels of CD3^(+)T,CD4^(+)T,CD8^(+)T,Th1 and Th2 cells in rat peripheral blood;ELISA was applied to detect IL-10,IL-2,TNF-α,IgG and IgM in serum;qRT-PCR and Western blot were applied to detect mRNA and protein expressions of SDF-1 and CXCR4.Results:Compared with control group,24-hour urine protein,BUN,Scr,TC,triglyceride(TG)contents,CD8^(+)T,Th1,Th1/Th2,IL-2,TNF-α,SDF-1,CXCR4 mRNA and protein expressions of rats in Model group were obviously in-creased,albumin(ALB)content,spleen index,thymus index,CD3^(+)T,CD4^(+)T,Th2 cell proportions,CD4^(+)T/CD8^(+)T,IL-10,IgG,and IgM levels were obviously reduced(P<0.05);compared with Model group,24-hour urine protein,BUN,Scr,TC,TG contents,CD8^(+)T,Th1,Th1/Th2,IL-2,TNF-α,SDF-1,CXCR4 mRNA and protein expressions of rats in Gal low,medium and high doses groups were gradually decreased,ALB content,spleen index,thymus index,CD3^(+)T,CD4^(+)T,Th2 cell proportions,CD4^(+)T/CD8^(+)T,IL-10,IgG and IgM levels were gradually increased(P<0.05);compared with high-dose Gal group,changes in above indicators in activator group of rats were obviously reversed(P<0.05).Conclusion:Gal may enhance T lymphocyte immune function by inhibiting SDF-1/CXCR4 pathway,thereby alleviating renal injury in NS rats.
作者
张秋霞
许春梅
林文静
章宇
林春
ZHANG Qiuxia;XU Chunmei;LIN Wenjing;ZHANG Yu;LIN Chun(Department of Nephrology,Longyan First Hospital Affiliated to Fujian Medical University,Longyan 364000,China)
出处
《中国免疫学杂志》
北大核心
2025年第8期1945-1950,共6页
Chinese Journal of Immunology
