RRx-001对吉兰-巴雷综合征大鼠模型的保护作用及机制研究  

Protective effect of RRx-001 on a rat model of Guillain-Barrésyndrome and related mechanism

作　　者：高远 李煜 武心语 杨慧 朱正杨 年娣 时鹏[1] GAO Yuan;LI Yu;WU Xinyu;YANG Hui;ZHU Zhengyang;NIAN Di;SHI Peng(Department of Neurology,The First Affiliated Hospital of Bengbu Medical College,Bengbu,Anhui 233004,China;Department of Nuclear Medicine,College of Laboratory Medicine,Bengbu Medical College,Bengbu,Anhui 233030,China)

机构地区：[1]蚌埠医学院第一附属医院神经内科,安徽蚌埠233004 [2]蚌埠医学院检验医学院核医学教研室,安徽蚌埠233030

出　　处：《国际神经病学神经外科学杂志》2023年第6期1-6,共6页Journal of International Neurology and Neurosurgery

基　　金：安徽省高校自然科学研究重点项目(KJ2020A0570);安徽省高校自然科学研究重大项目(KJ2021ZD0084);蚌埠医学院自然科学基金重点项目(2021byzd049);安徽省临床医学转化项目(202304295107020075);蚌埠医学院大学生创新创业训练计划项目(S202210367057)。

摘　　要：目的探讨RRx-001对实验性自身免疫性神经炎(EAN)的保护作用及机制的影响。方法采用人工合成P253~78肽段与完全弗氏佐剂混合免疫Lewis大鼠建立EAN模型,RRx-001腹腔注射给药。实验分为3组:对照组、模型组和实验组。通过检测大鼠体重和临床评分,评估病情进展。采用透射电镜观察坐骨神经脱髓鞘变化。检测血液异硫氰酸荧光素―右旋糖酐,评估肠道屏障通透性。检测肠道一氧化氮(NO)、谷胱甘肽(GSH)和超氧化物歧化酶(SOD),评估氧化应激水平。采用ELISA试剂盒检测白细胞介素(IL)-1β、IL-18和肿瘤坏死因子α(TNF-α)表达情况。采用流式细胞术分析CD3^(+)T细胞、CD3^(+)CD4^(+)T细胞、CD3^(+)CD8^(+)T细胞、CD4^(+)CD44H^(+)T细胞、CD4^(+)CD62L^(+)T细胞和CD11b^(+)F4/80^(+)巨噬细胞。结果与模型组相比,RRx-001可以减少EAN大鼠体重丢失、降低临床评分(P<0.05);缓解坐骨神经脱髓鞘;提高SOD活力,降低IL-1β和TNF-α表达水平,减轻肠道损伤而改善肠通透性(P<0.001);降低CD4^(+)T/CD8^(+)T淋巴细胞和CD11b^(+)F4/80^(+)巨噬细胞比例,提升CD3^(+)T淋巴细胞的比例(P<0.05)。结论RRx-001可以改善EAN大鼠临床症状,其机制可能与调节免疫细胞活化和抑制炎症因子释放有关,发挥对EAN大鼠的保护作用。Objective To investigate the protective effect of RRx-001 on experimental autoimmune neuritis(EAN)and related mechanism.Methods Lewis rats were immunized with a synthetic P253-78 peptide mixed with complete Freund’s adjuvant to establish a model of EAN,and RRx-001 was administered by intraperitoneal injection.The rats were divided into control group,model group,and experimental group.Body weight and clinical score were determined to assess disease progression;transmission electron microscopy was used to observe the demyelination of sciatic nerve;blood fluorescein isothiocyanate(FITC)-dextran level was measured to assess intestinal barrier permeability;the levels of nitric oxide(NO),glutathione(GSH),and superoxide dismutase(SOD)in the intestinal tract were measured to assess the level of oxidative stress;ELISA kits were used to measure the expression levels of interleukin-1β(IL-1β),interleukin-18(IL-18),and tumor necrosis factor-α(TNF-α);flow cytometry was used to analyze CD3^(+)T cells,CD3^(+)CD4^(+)T cells,CD3^(+)CD8^(+)T cells,CD4^(+)CD44H^(+)T cells,CD4^(+)CD62L^(+)T cells,and CD11b^(+)F4/80^(+)macrophages.Results Compared with the model group,RRx-001 reduced the weight loss and clinical score of EAN rats(P<0.05),alleviated sciatic nerve demyelination,and improved intestinal permeability by increasing the activity of SOD,reducing the expression levels of IL-1βand TNF-α,and alleviating intestinal damage(P<0.001);it also reduced the percentages of CD4^(+)T/CD8^(+)T lymphocytes and CD11b^(+)F4/80^(+)macrophages and increased the percentage of CD3^(+)T lymphocytes(P<0.05).Conclusions RRx-001 can improve the clinical symptoms of EAN rats and exert a protective effect on EAN rats possibly by regulating the activation of immune cells and inhibiting the release of inflammatory factors.

关 键 词：实验性自身免疫性神经炎 RRx-001 炎症因子 T淋巴细胞 巨噬细胞 大鼠 

分 类 号：R745[医药卫生—神经病学与精神病学]