热休克预处理对实验性自身免疫性脑脊髓炎神经细胞凋亡的影响及其机制研究  

Effects and mechanisms of heat shock preconditioning on apoptosis of neural cells in rats with experimental autoimmune encephalomyelitis

作　　者：张金凤[1,2] 黄榕[1] 徐俊[3] 金世杰[4] 杨于嘉[1] 

机构地区：[1]中南大学湘雅医院儿科,长沙410008 [2]佛山市顺德区妇幼保健院 [3]湖南省人民医院儿科,长沙410002 [4]湖南省儿童医院呼吸免疫科,长沙 410007

出　　处：《中华神经医学杂志》2008年第1期24-28,共5页Chinese Journal of Neuromedicine

基　　金：湖南省自然科学基金（02JJY3015）

摘　　要：目的观察热休克预处理（HSP）后实验性自身免疫性脑脊髓炎（EAE）大鼠热休克蛋白70（HSP70）和核因子-KB（NF-KB）的表达及对神经细胞凋亡的影响，探讨其对EAE模型的神经保护作用。方法36只Wistar大鼠随机分为对照组（CON），EAE组和HSP组。EAE组制作成EAE模型；HSP组先给予HSP，24h后再制作成EAE模型；CON组不行特殊处理。观察大鼠神经症状．进行神经功能评分。于免疫后14-17d处死动物，取脊髓行HE染色，检测HSP70、NFKB免疫组化表达及神经细胞的凋亡。结果CON组大鼠没有发病。与EAE组大鼠比较，HSP组大鼠发病率显著降低，起病时间显著延迟，神经功能评分显著降低（均P〈0．05）。EAE组体重增加值较CON组明显减低，HSP后大鼠体重增加值较EAE组显著增加（p〈0．05）。脊髓病理显示HSP组炎性病灶数较EAE组显著减少（p〈0．05）。HSP组与EAE组相比，脊髓内HSP70阳性细胞数显著增加，NF-KB阳性细胞数显著减少，神经细胞凋亡显著抑制（均P〈0．01）。结论HSP对EAE大鼠具有一定的神经保护作用，其机理可能与HSP70表达增加，NF—KB表达受抑制从而导致神经细胞凋亡减少有关。Objective To study the effects of heat shock preconditioning on expressions of heat shock protein 70 （HSP70） and nuclear factor-KB （NF-KB） and apoptosis of neural cells in rats with experimental autoimmune encephalomyelitis （EAE）. Methods A total of 36 Wistar rats were randomly divided into control （CON）, EAE and treatment groups. EAE animal models were induced in the guinea pig with myelin basic protein in group EAE; EAE models were induced 24 h after heat shock preconditioning in the treatment group; no special treatment was done for group CON. Neurological signs of rats were observed and their neurological function scores were evaluated. Rats were sacrificed during 14-17 d after immunization and their spinal cords were removed and stained with hematoxylin and eosin. Expressions of HSP70 and NF-kB were determined by immunohistochemistry and apoptosis of neural cells were measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） assay. Results There was no signs in group CON. Compared with the EAE group, the morbidity of the treatment group was evidently reduced, onset time was remarkably postponed and neurological function scores were noticeably decreased （P〈0.05, respectively）. Body weight increment in the EAE group was noticeably lower than that in the CON group and heat shock preconditioning evidently increased body weight increment （P〈0.05）. The number of inflammatory loci in HSP Groups was lower than that in the EAE group （P〈0.05）. Heat shock preconditioning evidently increased the number of intraspinal HSP70-positive cells, decreased the number of NF-KB-positive cells and inhibited apoptosis of neural cells, compared with the EAE group （P〈0.01, respectively）. Conclusion Heat shock preconditioning may exert some neuroprotective effects on rats with EAE, mechanisms of which might be involved with the decrease in apoptosis of neural cells caused by the increased expression of HSP70 and suppressed expression of NF-KB.

关 键 词：脑脊髓炎 自身免疫性 实验性 热休克预处理 热休克蛋白70 核因子-KB 细胞凋亡 

分 类 号：R744[医药卫生—神经病学与精神病学]