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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。
Objective To investigate the therapeutic effect and mechanism of Erythropoietin (EPO) on experimental autoimmune neuritis (EAN). Methods A total of 12 Lewis rats were randomly divided into EPO treatment group (n = 6) and PBS control group (n = 6). P257-81 peptide of rat peripheral nerve was used to induce acute EAN model. Body weight and nerve function score were measured daily until the end of experiment. EPO treatment started on the 7th day after immunization. On the 14th day (peak), the sciatic nerve of rats was taken and the inflammatory infiltration of T cells was observed by immunohistochemistry. On the 21st day (convalescence), the rat lymph nodes were taken and the relative expression of IFN-γ, IL-17, IL-4 and Foxp3 was detected by fluorescence quantitative PCR. Inhibition of EPO in lymphocyte proliferation assay was examined by radioactive 3H-TdR incorporation assay. Results The severity of EAN decreased significantly after EPO treatment. Immunohistochemistry showed that the infiltration of T cells in the peripheral nerve in the treatment group decreased. The expression of IFN-γ and IL-17 in the lymph node of the treatment group decreased with the increase of the expression of IL-4 and Foxp3 Increased expression; lymphocyte proliferation experiments showed that EPO dose-dependent inhibition of lymphocyte proliferation. Conclusions EPO has a significant therapeutic effect on EAN. This therapeutic effect may be related to the inhibition of inflammatory infiltration and proliferation of T cells by EPO, inhibition of inflammatory injury of Th1 / Th17 cytokines and promotion of immunosuppression of Th2 / Treg cytokines.