脱氢表雄酮对大鼠实验性自身免疫性神经炎的影响

目的探讨脱氢表雄酮（DHEA）对大鼠实验性自身免疫性神经炎（EAN）发病的影响及其机制。方法随机将36只Lewis大鼠分为DHEA 0.5mg治疗组、2mg治疗组和对照组。治疗组于注射牛周围神经髓磷脂（BPM）抗原乳剂后第5天开始每日皮下注射DHEA，对照组皮下注射相同体积的DHEA溶媒。观察各组发病时间及临床评分,检查疾病高峰期坐骨神经组织病理及干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）阳性反应细胞，检测引流淋巴结和脾脏单个核细胞增殖反应，检测培养上清TNF-α、IFN-γ、白介素-10（IL-10）含量。 结果两种剂量DHEA治疗组均能延迟EAN发病时间(P均<0.05)，减少坐骨神经炎性细胞浸润数目(P均<0.05)和IFN-γ、TNF-α阳性反应细胞数目(P均<0.05)，抑制BPM刺激T淋巴细胞增殖(P均<0.05)，降低培养上清中IFN-γ、TNF-α水平(P均<0.05)。2?mg治疗组疾病高峰期临床评分明显降低于对照组(P<0.05)。各组间 IL-10水平未显示明显差异（P>0.05）。结论DHEA可能通过抑制自身反应性T淋巴细胞增殖和促炎性细胞因子过度表达减轻EAN病情，2mg治疗组具有更明显的免疫治疗效果。

Effects of dehydroepiandrosterone on experimental autoimmune neuritis in Lewis rats

To explore the effects of dehydroepiandrosterone (DHEA) on the development of experimental autoimmune neuritis (EAN) and to explore its mechanism. Methods Thirty-six Lewis rats were randomly divided into the DHEA 0.5mg treatment group, the DHEA 2mg treatment group and the control group (n=12). The treatment groups were subcutaneously injected every day with DHEA and the control group was subcutaneously injected with the same volume of DHEA dissolvent from day 5 post-immunization (p.i.) to day 28 p.i. with bovine peripheral myelin（BPM）in Freund′s complete adjuvant (CFA). The effects were assessed in terms of appearance of clinical signs, clinical score, histopathology and IFN-γ and TNF-α positive cells in sciatic nerve sections, and T-cell proliferation and inflammatory cytokines (IFN-γ,TNF-α and IL-10) synthesis by draining lymph nodes and spleen cells. ResultsRats receiving DHEA in the two different therapeutic regimens displayed a significant delay in onset (P<0.05 and P<0.05), a decreased inflammatory cell infiltration into the PNS (P<0.05,P<0.05) and decreased numbers of IFN-γ and TNF-α expression cells in the PNS(P<0.05 and P<0.05 ), and reduced BPM stimulated T cell proliferation(P<0.05 and P<0.05) and IFN-γ and TNF-α secretion in the draining lymph node and spleen (P<0.05, P<0.05) compared to the control group. Only the DHEA 2mg treatment group had the significant differences of supernatant IL-10 were found among the different treatment and control groups（P>0.05）.ConclusionAdministration of exogenous DHEA ameliorates the severity of EAN, presumably by suppressing the proliferation of auto-reactive T-cells and moderating the over-expression of pro-inflammatory cytokines. DHEA 2mg therapy is more effective than DHEA 0.5mg therapy.