促红细胞生成素对实验性自身免疫性神经炎大鼠的治疗作用及机制  

Erythropoietin treatment ameliorates experimental autoimmune neuritis

作　　者：罗邦伟[1] 张志仁[1] 姜曼[1] 孙怡[1] 吴玉章[1] 

机构地区：[1]第三军医大学基础部免疫学教研室,重庆400038

出　　处：《免疫学杂志》2011年第11期921-925,共5页Immunological Journal

基　　金：国家自然科学基金(81070954);第三军医大学校级科研课题(2010xhg04)

摘　　要：目的研究促红细胞生成素(Erythropoietin,EPO)对实验性自身免疫性神经炎(Experimental autoimmune neuritis,EAN)的治疗作用及机制。方法将Lewis大鼠共12只随机分的为EPO治疗组6只和PBS对照组6只,使用大鼠外周神经P257-81肽段诱发急性EAN模型,每天测量体重和神经功能评分至实验结束,免疫后第7天开始进行EPO治疗。第14天(高峰期)取大鼠坐骨神经,用免疫组化染色观察T细胞炎症浸润。第21天(恢复期)取大鼠淋巴结,用荧光定量PCR方法检测IFN-γ、IL-17、IL-4和Foxp3的相对表达。使用放射性3H-TdR掺入法检测淋巴细胞增殖实验中EPO的抑制作用。结果 EPO治疗后大鼠EAN严重度显著降低;免疫组化显示治疗组外周神经T细胞浸润减少;荧光定量PCR结果显示治疗组淋巴结中IFN-γ和IL-17表达降低,而IL-4和Foxp3表达增加;淋巴细胞增殖实验表明EPO剂量依赖地抑制淋巴细胞增殖。结论 EPO对EAN有明显治疗作用,这种治疗作用可能与EPO抑制T细胞的炎症浸润和增殖反应,抑制Th1/Th17类细胞因子炎症损伤,促进Th2/Treg类细胞因子免疫抑制作用有关。In this study,we aim to evaluate the therapeutic effects and the potential mechanism of erythropoietin（EPO） in treating experimental autoimmune neuritis（EAN）,a rat model of Guillain-Barre syndrome（GBS）.Total of 12 rats were randomly divided into EPO treatment group（6 rats） and PBS（6 rats） control group.P257-81 peptide,a rat peripheral nerve myelin associated protein,was used to induce the acute EAN model.Body weight and neurological score of experimental rats were daily recorded from the beginning.EPO treatment began from day 7 after immunization.On day 14（peak period）,immunohistochemistry staining was used to observe the T-cell inflammatory infiltrate in the sciatic nerve.On day 21（recovery period）,mRNA expressions of IFN-γ,IL-17,IL-4 and the Foxp3 in lymphnode were detected by real time-PCR.In the subsequent in vitro lymphocyte proliferation experiment,radioactive 3H-TdR incorporation assay was used to detect the inhibition of EPO on ConA-stimulated cell proliferation.We found that EPO treatment effectively ameliorated EAN severity and improved EAN recovery;immunohistochemistry result showed that T-cell infiltration in sciatic nerve was reduced by EPO treatment at the peak time.Real time PCR results showed that in lymphnode of the recovery period,IFN-γ and IL-17 mRNA expressions were diminished in EPO treatment group while IL-4 and Foxp3 was increased;3H-TdR incorporation assay showed a dose-dependent inhibition of EPO on ConA-stimulated cell proliferation.Above results imply that EPO can ameliorates EAN by inhibiting T cell infiltrate in peripheral nerve,regulating T cell cytokine secretion and suppressing lymphocyte proliferation.Therefore,EPO is a prospective candidate in treating EAN.

关 键 词：促红细胞生成素 实验性自身免疫性神经炎 治疗作用 免疫抑制 

分 类 号：R745.43[医药卫生—神经病学与精神病学]