摘要
目的通过体内外实验研究鸢尾素irisin对病毒性心肌炎小鼠的保护作用及其免疫调节作用。方法体外分离培养乳鼠心肌细胞,并经柯萨奇B3病毒(CVB3)感染诱导心肌细胞凋亡,利用流式细胞术检测各组心肌细胞经10、50、100μg/L的irisin作用后细胞凋亡情况。构建CVB3接种感染Balb/c小鼠的体内病毒性心肌炎模型,并分成空白对照组、模型组和10、50、100μg/kg irisin蛋白治疗处理的irisin作用组,利用流式细胞术检测各组小鼠外周血中相关免疫细胞(NK、CD4^(+)T、CD8^(+)T、CD4^(+)/CD8^(+))和淋巴细胞中Treg和Th17细胞比例变化;ELISA方法检测各组小鼠心肌组织中炎性相关细胞因子水平的变化。结果与对照组相比,模型组心肌细胞凋亡率显著上升,而各低、中、高浓度irisin作用组心肌细胞凋亡率逐渐下降(P<0.05);与对照组相比,模型组小鼠的NK、CD4^(+)T细胞比例、CD4^(+)/CD8^(+)比值均显著下降(均P<0.05),CD8^(+)T、Treg、Th17细胞比例和相关炎性细胞因子水平则均显著上升(均P<0.05);经过不同浓度irisin治疗作用后,各组病毒性心肌炎小鼠的NK、CD4^(+)T细胞比例、CD4^(+)/CD8^(+)比值逐渐上升,且CD8^(+)T、Treg、Th17细胞比例和相关炎性细胞因子水平均逐渐下降(均P<0.05)。结论鸢尾素irisin能够抑制CVB3病毒诱导的病毒性心肌炎心肌细胞凋亡,并可通过调控Treg/Th17细胞比例来改善病毒性心肌炎机体的免疫反应。
This study was performed to investigate the protective effect and immunoregulatory effect of irisin in mice with viral myocarditis by using in vitro and in vivo experiments.In vitro,neonatal rat cardiomyocytes were isolated and infected with Coxsackie B3 virus(CVB3)to induce apoptosis,and flow cytometry was used to determine the apoptosis of cardiomyocytes in each group after 10,50,and 100μg/L of irisin.An in vivo viral myocarditis model of CVB3 inoculated and infected Balb/c mice was constructed and divided into blank control group,model group,and 10,50,100μg/kg irisin groups;and then flow cytometry was used to determine the proportions of the related immune cells(NK,CD4^(+)T,CD8^(+)T)in the peripheral blood of mice of each group,while ELISA was performed to detect inflammatory cytokines levels.Compared with the control group,the apoptosis rate of cardiomyocytes in the model group increased significantly,whereas the apoptosis rate of cardiomyocytes in each irisin treated group gradually decreased(P<0.05).Compared with the control group,the frequency of NK cells,CD4^(+)T cells,and CD4^(+)/CD8^(+)ratio in the model group were significantly decreased(all P<0.05),while the levels of CD8^(+)T cells,Treg cells,Th17 cells and inflammatory cytokines were significantly increased(all P<0.05)in the model group.Compared with the model group,the proportion of NK cells,CD4^(+)T cells and CD4^(+)/CD8^(+)ratio gradually increased(all P<0.05)in the different irisin treated groups,and the levels of CD8^(+)T cells,Treg cells,Th17 cells and inflammatory cytokines gradually decreased(all P<0.05).In conclusion,irisin can inhibit the apoptosis of cardiomyocytes in CVB3 virus-induced viral myocarditis and can improve immune responses in the body with viral myocarditis by regulating Treg/Th17 cells rate.
作者
王芳娟
龙雪蛟
胡巨龙
WANG Fangjuan;LONG Xuejiao;HU Julong(Department of Cardiology,First Affiliated Hospital of Army Military Medical University,Chongqing 400038,China;Department of Plastic Surgery,Xingrong Plastic Surgery Hospital,Chongqing 430056,China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2021年第8期652-658,共7页
Immunological Journal
