雷公藤多苷对CVB3诱导的小鼠病毒性心肌炎的作用研究  

Effect of Tripterygium wilfordii polyglycosides on viral myocarditis induced by CVB3 in mice

作　　者：宋晓英[1] 于震 于文霞 Song Xiaoying;Yu Zhen;Yu Wenxia(Clinical Lab,Qingdao Municipal Hospital,Qingdao 266001,China)

机构地区：[1]青岛市市立医院医学检验学部,山东青岛266001

出　　处：《国际免疫学杂志》2022年第4期373-380,共8页International Journal of Immunology

摘　　要：目的探讨雷公藤多苷对B组柯萨奇病毒3(Coxsackievirus B group 3,CVB3)诱导的病毒性心肌炎(viral myocarditis,VMC)的治疗作用及相关机制。方法细胞学实验观察雷公藤多苷对CVB3感染HeLa细胞模型的影响;建立CVB3诱导的Balb/C小鼠VMC模型,根据雷公藤多苷灌胃给药剂量将小鼠随机分为4组[空白对照组、高剂量组(20 mg/kg)、中剂量组(10 mg/kg)、低剂量组(5 mg/kg)]。通过苏木精-伊红染色(hematoxylin-eosin staining,HE)检测不同剂量药物作用下,动物模型心肌组织的病变及免疫细胞浸润情况;利用酶联免疫试验检测不同药物剂量组外周血心肌酶表达水平,并利用流式细胞技术检测各组外周血中T细胞亚型的凋亡情况;利用实时定量PCR的方法检测不同剂量组心室肌组织内细胞因子的表达水平。结果成功构建Balb/C小鼠VMC模型,雷公藤多苷治疗显著缓解CVB3引起的小鼠心肌免疫浸润损伤。与对照组相比,低、中、高剂量雷公藤多苷显著增加VMC小鼠外周血CD4^(+)T淋巴凋亡比例,差异具有统计学意义[(12.26±1.92)%,(19.07±1.85)%,(20.92±3.30)%比(8.28±1.13)%,F值分别为19.06、148.64、78.46,Bonferroni校正P值均<0.05]。与对照组相比,高剂量雷公藤多苷对CD8^(+)T淋巴细胞凋亡比例也起到显著抑制作用[(16.65±2.30)%比(8.83±1.81)%,F=42.88,Bonferroni校正P<0.05],低、中剂量雷公藤多苷增加VMC小鼠外周血CD8^(+)T淋巴凋亡比例不明显(P>0.05)。中、高剂量药物组VMC小鼠脾脏淋巴细胞在ConA刺激下,淋巴细胞增殖率均低于对照组[(0.76±0.05),(0.75±0.04)比(0.87±0.07),F值分别为10.38、16.09,Bonferroni校正P值均<0.05]。此外,雷公藤多苷治疗在病毒感染第10天对VMC小鼠心肌组织肿瘤坏死因子a(tumor necrosis factor-a,TNF-a)、白细胞介素(interleukin,IL)-6、IL-12和IL-17等促炎因子表达产生抑制作用,20 mg/kg剂量雷公藤多苷组TNF-a、IL-6、IL-12、IL-17在VMC模型心室肌平均表达水平分别�Objective To study the therapeutic effects of tripterygium wilfordii polyglycosides on viral myocarditis(VMC)induced by Coxsackievirus B group 3(CVB3)and related immunological mechanisms.Methods Cytological experiments were conducted to observe the effect of Tripterygium wilfordii polyglycoside on HeLa cell model infected by CVB3;The mouse model of VMC induced by CVB3 was established.The mice were randomly divided into 4 groups(blank control group,high dose group(20 mg/kg),medium dose group(10 mg/kg)and low dose group(5 mg/kg))according to the dose of Tripterygium wilfordii glycosides administered by gavage.The pathological changes and immune cell infiltration of myocardial tissue in the animal model were detected by hematoxylin-eosin staining(HE)under the effect of different doses of drugs;TCID50 test was used to detect the viral load in myocardium of each group;Enzyme linked immunosorbent assay was used to detect the expression of myocardial enzymes in peripheral blood,and flow cytometry was used to detect the apoptosis of T cell subtypes in peripheral blood;Real time quantitative PCR was used to detect the expression of cytokines in ventricular muscle tissue of different dose groups.Results The mouse VMC model was successfully constructed.Tripterygium wilfordii glycoside treatment significantly alleviated the myocardial immune infiltration injury of VMC model in CVB3 Balb/C mice caused by CVB3.Compared with the control group,low,medium and high doses of Tripterygium wilfordii glycoside increased the percentage of CD4^(+)T lymphoid apoptosis in peripheral blood of VMC mice,The difference was statistically significant[(12.26±1.92)%,(19.07±1.85)%,(20.92±3.30)%vs(8.28±1.13)%,F values were 19.06,148.64 and 78.46,respectively,Bonferroni corrected P values between groups were<0.05].Compared with the control group,high-dose Tripterygium wilfordii polyglycoside also inhibited the apoptosis ratio of CD8^(+)T lymphocytes[(16.65±2.30)%vs(8.83±1.81)%,F value was 42.88,Bonferroni corrected P value<0.05],and medium and

关 键 词：雷公藤多苷 B组柯萨奇病毒 病毒性心肌炎 细胞免疫 

分 类 号：R285.5[医药卫生—中药学]