阿托伐他汀诱导BMDCs源性外泌体对EAMG模型大鼠临床症状的缓解及与自然杀伤细胞和自然杀伤T细胞的关系  

Clinical relief of BMDCs derived exosomes induced by atorvastatin in EAMG rats and its correlation with natural killer cells and natural killer T cells

作　　者：陈海青 王雪梅[2] Chen Haiqing;Wang Xuemei(Department of Critical Care Medicine,981st Hospital,People's Liberation Army,Chengde Hebei 067000;不详)

机构地区：[1]河北省承德市中国人民解放军联勤保障部队第九八一医院重症医学科,067000 [2]河北省承德市中国人民解放军联勤保障部队第九八一医院重症质控科,067000

出　　处：《卒中与神经疾病》2020年第3期312-315,共4页Stroke and Nervous Diseases

摘　　要：目的分析阿托伐他汀诱导骨髓来源树突状细胞(BMDCs)源性外泌体对实验性自身免疫性重症肌无力(EAMG)模型大鼠临床症状的缓解及与自然杀伤细胞和自然杀伤T细胞的关系。方法分别采用二甲基亚砜、阿托伐他汀与BMDCs进行共培养,分别设置对照组(二甲基亚砜与BMDCs共培养)和实验组(阿托伐他汀与BMDCs共培养),通过流式细胞术检测2组BMDCs表面共刺激分子的表达水平;通过梯度离心法提取2组BMDCs源性外泌体,将其注射于EAMG大鼠体内,实验组给予阿托伐他汀,对照组未进行任何治疗,记录2组大鼠临床症状评分;采用流式细胞术测定2组大鼠淋巴结单个核细胞中自然杀伤细胞和自然杀伤T细胞的比例。结果实验组BMDCs表面共刺激分子CD80和CD86表达水平较对照组显著下降(P<0.01),而2组主要组织相容性复合体Ⅱ(MHC-Ⅱ)分子表达水平无明显差异(P>0.05);实验组免疫2、4、6周后临床症状评分较对照组均明显降低(P<0.01)。与对照组比较,实验组大鼠淋巴结单个核细胞中自然杀伤细胞的比例明显升高(P<0.01),而2组大鼠淋巴结单个核细胞中自然杀伤T细胞的比例无明显差异(P>0.05)。结论阿托伐他汀诱导BMDCs分泌源性外泌体可有效减轻EAMG大鼠临床症状,其作用机制可能与提高大鼠淋巴结单个核细胞中自然杀伤细胞的比例有相关。Objective To analyze the clinical relief of atorvastatin induced myeloid dendritic cells(BMDCs) derived exosomes in experimental autoimmune myasthenia gravis(EAMG) rats and its relationship with natural killer cells and natural killer T cells.Methods BMDCs were co-cultured with dimethyl sulfoxide and atorvastatin respectively, as control group(dimethyl sulfoxide co-cultured with BMDCs) and experimental group(atorvastatin co-cultured with BMDCs) respectively. The expression levels of surface costimulatory molecules in BMDCs of the two groups were detected by flow cytometry. Source exosomes in BMDCs of the two groups were extracted by gradient centrifugation and injected into EAMG rats. Atorvastatin was given to the experimental group and no treatment was given to the control group. Clinical symptom scores of the two groups were recorded. Flow cytometry was used to determine the proportion of nk cells and nk T cells in the mononuclear cells of the lymph nodes of the two groups.Results Compared with the control group, BMDCs stimulating molecules CD80 and CD86 expression levels on the surface in the experimental group were decreased significantly(P<0.01), and there was no significant difference between major histocompatibility complex Ⅱ(MHC-Ⅱ) molecular expression levels of two groups(P>0.05). The clinical symptom scores of the experimental group for 2, 4 and 6 weeks after immunization were significantly lower than those of the control group(P<0.01). Compared with the control group, the proportion of natural killer cells in the mononuclear cells of lymph nodes in the experimental group was significantly increased(P<0.01). There was no significant difference between natural killer T cells of the two groups(P>0.05).Conclusion BMDCs secretory exosomes induced by atorvastatin could effectively alleviate the clinical symptoms of EAMG in rats, and its mechanism might be closely related to the increase of the proportion of natural killer cells in rat lymph node mononuclear cells.

关 键 词：实验性自身免疫性重症肌无力 阿托伐他汀 髓源树突细胞 自然杀伤细胞 自然杀伤T细胞 

分 类 号：R746.1[医药卫生—神经病学与精神病学]