摘要
目的研究沙利度胺对实验性自身免疫性脑脊髓炎(EAE)的治疗作用及神经免疫机制。方法采用豚鼠脊髓匀浆免疫诱导SD大鼠制作EAE模型。在免疫诱导当天开始,分别给予15、30、60mg/kg沙利度胺,溶剂组给予无菌溶剂,空白对照组不予给药,每日监测行为学评分,至免疫诱导的第20天统一处死。常规病理染色检测中枢炎症水平,流式细胞术检测中枢CD4^+T细胞浸润水平以及CD4^+CD25^+Treg细胞比例,Elisa检测血清INF-γ与TNF-α蛋白浓度。结果与溶剂组比较,给予15mg/kg沙利度胺大鼠EAE行为学评分、中枢炎症程度、CD4^+T淋巴细胞浸润水平,血清INF-γ浓度均有下降趋势但差异无统计学意义(P>0.05),而TNF-α浓度下降差异有统计学意义(P<0.05)。给予30、60mg/kg沙利度胺均可使行为学评分下降,中枢炎症减轻,中枢CD4^+T细胞浸润减少,血清INF-γ,TNF-α浓度降低。流式细胞术还发现沙利度胺可促进中枢Treg比例上调,差异有统计学意义。结论沙利度胺对大鼠EAE的治疗作用可能与促进Treg细胞向中枢募集有关。
Objective To investigate the effect of thalidomide on experimental autoimmune encephalomyelitis（EAE）in rats and its related mechanisms. Methods SD rates were injected with spinal cord homogenate of guinea pig（EAE group） or solvent（control group）,then the rats were treated with thalidomide at different doses（15 mg/kg, 30 mg/kg, 60 mg/kg）. The clinic scores of EAE were assessed daily until animals were sacrificed. All rats were sacrificed at d20 after model induced and paraffin sections were prepared and stained with hematoxylin-eosin. Serum INF-γ and TNF-α levels were measured by ELISA. The spinal cord infiltrating CD4~＋T cells and CD4~＋CD25~＋T cells were determined by flow cytometry. Results Thalidomide 15 mg/kg did not effectively reduce the severity of EAE, but reduced the TNF-αprotein levels. Thalidomide 30 mg/kg and 60 mg/kg reduced the clinic score of EAE, the inflammation in the spinal cord, the number of infiltrating CD4~＋T cells and the INF-γ, TNF-α protein levels. And thalidomide 60 mg/kg promoted CD4~＋CD25~＋T cell recruitment into central nervous system. Conclusion Thalidomide alleviated the severity of EAE in rats, which may be related to the promotion of CD4~＋CD25~＋T cell recruitment into central nervous system.
出处
《浙江医学》
CAS
2017年第22期1957-1960,1980,共5页
Zhejiang Medical Journal
基金
浙江省基础公益研究计划项目(LGF18H090018)
绍兴市人民医院青年科研基金项目(2017A10)
