胸腺五肽治疗实验性自身免疫性脑脊髓炎的实验研究

Study on the treatment of experimental autoimmune encephalomyelitis in rats by thymopentin

目的应用胸腺五肽（thymopentin，TP-5）干预实验性自身免疫性脑脊髓炎（experiment autoimmue encephalomyelitis，EAE）大鼠，探讨该药物对EAE的治疗作用及其机制。方法以豚鼠全脊髓匀浆（guinea pig spinal cord homogenate，GPSCH）与完全弗氏佐剂（CFA）为抗原免疫Wistar大鼠建立EAE模型。Wistar大鼠随机分为正常对照组、EAE组、地塞米松（dexamethasone，DXM）组、TP-5小剂量组、TP-5大剂量组。采用双抗体夹心ELISA法检测Wistar大鼠免疫后7、14、21d不同时间点血清中IL-12、IL—10的含量。结果与EAE组和TP-5大剂量组比较，TP-5小剂量组和DXM组大鼠的发病率和临床评分显著性降低（P〈0．01）；DXM组大鼠的发病率和临床评分低于TP-5小剂量组（P〈0．01）。各个时间点EAE组、DXM组、TP-5小剂量组、TP-5大剂量组IL-12含量均较正常对照组明显升高（P〈0．01），免疫后14、21dDXM组和TP-5小剂量组IL-12水平比EAE组低（P〈0．01）；免疫后14、21dDXM组、TP-5小剂量组IL-10水平与其余3组比较明显升高（P〈0．01）。结论TP-5对EAE有保护作用，其作用机制可能与上调IL-10水平以及下调IL-12水平有关，通过双向调节作用逆转TH1／TH2失衡。

Objective To investigate the therapeutic effects of thymopentin（TP-5） for the experimental autoimmune encephalomyelitis （EAE） in rats. Methods The EAE model was established in Wistar rats immunized with fresh guinea pig spinal cord homogenate （GPSCH） and complete Freund＇s adjuvant （CFA）. Wistar rats were divided randomly into five groups： normal control group, EAE group, dexamethasane （DXM） group, low dose TP-5 treated group, high dose TP-5 treated group. The levels of IL-12 and IL- 10 in serum of Wistar rats were detected by sandwich-ELISA on day 7, 14 and 21 post immunization. Results Morbidity and clinical score of low dose TP-5 treated group and DXM group were significantly lower than those of EAE group and high dose TP-5 treated group（ P 〈 0.01 ）. Morbidity and clinical score of DXM group were significantly lower than those of low dose of TP-5 treated group （P 〈 0.01 ）. The levels of IL-12 of EAE group, DXM group,low dose TP-5 treated group and high dose TP-5 treated group were significantly higher than that of normal control group at each time point （ P 〈 0.01 ）. The levels of IL-12 of DXM group and low dose TP-5 treated group were significantly lower than that of EAE group （ P 〈 0. 01 ）, meanwhile the levels of IL-10 of DXM group and low dose TP-5 treated group were significantly higher than that of the rest groups on day 14 and 21 post immunization （P 〈 0.01 ）. Conclusion TP-5 has protective effects on EAE, and its functional mechanism may be associated with down-regulation of IL-12 as well as up-regulation of IL- 10, so as to reverse the imbalance of TH1/TH2 responses by bidirectional regulation.