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目的建立 P2多肽诱导的实验性自身免疫性神经炎(EAN)大鼠模型,探讨 Th_1/Th_2型细胞因子在 EAN 发病机制中的作用。方法实验组用100μg或200μg P2_(57-81)多肽加完全弗氏佐剂(FCA)免疫 Lewis 大鼠,对照组单用 FCA 免疫,致敏后每日对大鼠进行临床评分,比较高峰期最高评分。致敏第14天测定淋巴结细胞培养液上清干扰素(IFN)-γ、IL-4及 IL-10的含量,并进行坐骨神经病理学检查。结果实验大鼠瘫痪高峰期最高评分 P2_(57-81)200μg组(3.6±0.3)显著高于100μg组(2.2±0.6,P<0.01);P2_(57-81)200μg组大鼠病程显著长于100μg组;IFN-γ含量,两组实验大鼠均显著高于对照组[分别为(530.6±91.7)、(806.3±132.4)和(35.0±5.9)pg/ml,均 P<0.01],而P2_(57-81) 200μg组显著高于100μg组(P<0.01);IL-4和 IL-10含量,P2_(57-81)100μg组均显著高于对照组(均 P<0.01),P2_(57-81)200μg组显著低于对照组(P<0.05,P<0.01);坐骨神经病理可见 EAN 急性期以炎性细胞浸润为主,P2_(57-81)200μg组慢性期无炎性细胞浸润,而表现为多发性局灶性脱髓鞘和神经纤维崩解未恢复。结论 EAN 临床表现随致敏原 P2_(57-81)多肽剂量增加而加重;在 EAN 急性期,IFN-γ水平与 EAN 临床表现大致平行;EAN 疾病具有自限性可能与 IL-4和 IL-10水平增高有关,而疾病迁延可能与 IL-4和 IL-10水平降低有关。
Objective To establish a rat model of experimental autoimmune neuritis (EAN) induced by P2 polypeptide and investigate the role of Th1 / Th2 cytokines in the pathogenesis of EAN. Methods In the experimental group, Lewis rats were immunized with 100μg or 200μg P257-81 polypeptide plus complete Freund’s adjuvant (FCA). The control group was immunized with FCA alone. After sensitization, the rats were scored daily to compare the peak period The highest score. On the 14th day after sensitization, the levels of IFN-γ, IL-4 and IL-10 in lymph node cell culture medium were determined and sciatic neuropathological examination was performed. Results The peak score of the rats at the peak of paralysis in experimental group was significantly higher than that of 100μg group (2.2 ± 0.6, P <0.01) on the P2_ (57-81) 200μg group (3.6 ± 0.3) 100μg group; IFN-γcontent was significantly higher in the two experimental groups than in the control group [(530.6 ± 91.7), (806.3 ± 132.4) and (35.0 ± 5.9) pg / ml, The content of IL-4 and IL-10 in P2_ (57-81) 200μg group was significantly higher than that in 100μg group (P <0.01) (57-81) 200μg group was significantly lower than that of the control group (P <0.05, P <0.01). Sciatic nerve pathology showed inflammatory cell infiltration in the EAN acute phase, and no inflammatory cells in the P2_ (57-81) 200μg chronic phase Infiltration, which showed multiple focal demyelination and collapse of nerve fibers is not restored. Conclusions The clinical manifestations of EAN aggravate with the increase of dose of allergen P2 57-81 polypeptide. In the acute phase of EAN, the level of IFN-γ is roughly parallel with the clinical manifestations of EAN. Self-limiting EAN disease may be associated with IL-4 and IL- 10 levels related to increased, and disease progression may be associated with lower IL-4 and IL-10 levels.