人参皂苷Rg1抑制小鼠实验性自身免疫性脑脊髓炎的作用及免疫机制
Role and Immune Mechanism of Ginsenoside Rg1 in Inhibiting Experimental Autoimmune Encephalomyelitis in Mice
  
DOI:
中文关键词:  人参皂苷  自身免疫性脑脊髓炎  多发性硬化  辅助性T细胞  调节性T细胞
英文关键词:Ginsenoside Rg1  Autoimmune encephalomyelitis  Multiple sclerosis  Helper T cell  Regulatory T cell
基金项目:国家自然科学基金项目(81673716);安徽省自然科学基金青年项目(1808085QH244);中央高校基本科研业务费专项资金项目(WK9110000037)
作者单位
徐 文,周 妍,朱国旗 1.中国科学技术大学附属第一医院神经内科安徽 合肥 2300002.安徽省儿童医院儿保科安徽 合肥 2300513.安徽中医药大学新安医学教育部重点实验室,安徽 合肥 230038 
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中文摘要:
      目的 观察人参皂苷Rg1对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis, EAE)的抑制作用及其对脾淋巴细胞T细胞亚群和外周血细胞因子水平的影响。方法 采用C57BL/6小鼠皮下多点注射MOG35-55、百日咳毒素的方法复制EAE模型。将EAE小鼠随机分为模型组,人参皂苷Rg1低、中、高剂量组,同时设置正常对照组,每组6只。首次免疫后第10天予以不同剂量Rg1腹腔注射,连续给药14 d。第35天处死小鼠后取脊髓,观察各组小鼠脊髓炎症细胞浸润和脱髓鞘等病理变化,采用流式细胞仪检测小鼠脾淋巴细胞Th1、Th17、Treg细胞亚群,采用ELISA法检测外周血白细胞介素(interleukin,IL)-17A、干扰素γ(interferon gamma, IFN-γ)、IL-6、IL-10水平。结果 与模型组比较,人参皂苷Rg1低、中、高剂量组小鼠神经症状评分显著下降(P<0.05),脊髓炎症细胞浸润评分和脱髓鞘评分显著降低(P<0.05),脾淋巴细胞CD4+、CD8+、Th1、Th17 T细胞亚群比例显著降低(P<0.05),Treg(CD4+CD25+FoxP3+)比例显著升高(P<0.05),外周血IFN-γ、IL-17A、IL-16水平显著降低(P<0.05),IL-10水平显著升高(P<0.05),人参皂苷Rg1的作用呈现明显的剂量依赖性。结论 人参皂苷Rg1可显著改善EAE小鼠的临床症状,减轻中枢神经系统脱髓鞘和炎症细胞浸润,其作用可能与调控Th17、Th1、Treg细胞亚群失衡,抑制炎症细胞因子表达相关。
英文摘要:
      Objective To investigate the role of ginsenoside Rg1 in inhibiting experimental autoimmune encephalomyelitis (EAE) and its influence on T lymphocyte subsets in the spleen and cytokines in peripheral blood. Methods A mouse model of EAE was established by subcutaneous multi-point injection of MOG35-55 and pertussis toxin. The EAE mice were randomly divided into model group and low-, middle-, and high-dose ginsenoside Rg1 groups, and a normal control group was also established, with 6 mice in each group. On day 10 after first immunization, the mice were given intraperitoneal injection of ginsenoside Rg1 at different doses for 14 consecutive days. The mice were sacrificed on day 35, and the spinal cord was collected to observe pathological changes such as inflammatory cell infiltration and demyelination. Flow cytometry was used to measure Th1, Th17, and Treg subsets in the mouse spleen, and ELISA was used to measure the levels of interleukin-17A (IL-17A), interferon-γ (IFN-γ), interleukin-6 (IL-6), and interleukin-10 (IL-10) in peripheral blood. Results Compared with the model group, the low-, middle-, and high-dose ginsenoside Rg1 groups had significant reductions in the score of nerve symptoms (P<0.05), the scores of inflammatory cell infiltration and demyelination in the spinal cord (P<0.05), and the percentages of CD4+, CD8+, Th1, and Th17 lymphocyte subsets in the spleen (P<0.05) and a significant increase in the percentage of Treg (CD4+CD25+FoxP3+) (P<0.05), as well as significant reductions in the levels of IFN-γ, IL-17A, and IL-16 in peripheral blood (P<0.05) and a significant increase in the level of IL-10 (P<0.05). Ginsenoside Rg1 exerted an effect in a significant dose-dependent manner. Conclusion Ginsenoside Rg1 can significantly improve clinical symptoms and reduce demyelination and inflammatory cell infiltration in the central nervous system in EAE mice, possibly by regulating the imbalance of Th17, Th1, and Treg subsets and inhibiting the expression of inflammatory cytokines.
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