摘要
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-αI、FN-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,2 mg治疗组具有更明显的免疫治疗效果。
Objective To explore the effects of dehydroepiandrostemne （DHEA） on the development of experimental autoimmune neuritis （FAN） and to explore its mechanism. Methods Thlrty-six Lewis rats were randomly divided into the DHEA 0.5 mg treatment group, the DHEA 2mg treatment group and the control group （ n = 12）. The treatment groups were subcutaneously in- jected every day with DHEA and the control group was subcutaneously injected with the same volume of DHEA dissolvent from day 5 pest-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. Results Rats 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 infdtration 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 prolif- eration（ P 〈 0.05 and P 〈 0.05） and IFN-γ and TNF-αsecretion in the draining lymph node and spleen （ P 〈 0.05, P 〈 0.05） compared to the control group. Only the DHEA 2mg tav.atment group had the peak clinical score decreased （P〈0.05）. No significant differences of supematant IL-10 were found among the different treatment and control groups （ P 〉 0.05）. Conclusion Administration 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.
出处
《山东大学学报（医学版）》
CAS
北大核心
2008年第9期837-841,共5页
Journal of Shandong University:Health Sciences
基金
山东省自然科学基金资助项目(Y2007C169)
