热应激对大鼠轴索损伤的保护作用

目的观察轴索损伤后相应的神经元及少突胶质细胞热休克蛋白70(HSP70)表达的变化及热应激对其表达的影响,探讨HSP70的神经保护作用. 方法 57只雄性Wistar大鼠随机分为正常对照组(A组,3只)、单纯视神经牵拉伤组(B组,18只)、单纯热应激处理组(C组,18只)和热应激预处理牵拉伤组(D组,18只).对B组大鼠右侧视神经施予牵拉,对C组大鼠施予热应激处理,D组大鼠热应激预处理24 h后再对右侧视神经施予牵拉,B、C、D组分别在4,8,16 h、1,3,5 d各处死3只大鼠.光镜下观察视神经、视网膜神经节细胞(RGCs)、视神经少突胶质细胞(OLs)的形态学变化,免疫组化染色检测RGCs及OLs HSP70表达情况. 结果牵拉伤后视神经轴索、RGCs及OLs的形态发生明显的病理变化,热应激预处理再致伤后上述病理改变有显著改善.单纯牵拉伤和单纯热应激处理均可使RGCs及OLs HSP70的表达增加,而热应激预处理再致伤使HSP70的表达明显增强,高峰表达时间提前,维持时间延长. 结论神经元及胶质细胞共同参与了轴索损伤后的病理过程.热应激能使HSP70表达增强、提前和延长,提高其神经保护作用.增强内源性神经保护作用是弥漫性轴索损伤(DAI)治疗的新途径.

Neuroprotective effects of heat stress on axonal injury

Objective To investigate the expressions of heat shock protein 70 (HSP70) in neurons and oligodendrocytes after the stretch injury and the effects of heat stress on HSP70 expression and explore neuroprotective effect of HSP70 on axonal injury. Methods Fifty-seven male Wistar rats were randomly divided into four groups: control group (Group A with three rats), stretch-only group (Group B with 18 rats), heat stress-only group (Group C with 18 rats) and heat stress pretreatment plus stretch group (Group D with 18 animals). Stretch injury was induced in the right optic nerves of rats in Group B. Heat stress was applied to animals of Group C. Animals in Group D were subjected to the same stretch injury as Group B posterior to the heat stress similar to Group C. Three animals respectively from each group of Group B, Group C and Group D were killed at 4, 8 and 16 hours, 1, 3 and 5 days, respectively. Morphological changes of optic nerves, retinal ganglion cells (RGCs) and oligodendrocytes (OLs) in optic nerves after stretch injury were examined under light microscope; and expressions of OLs HSP70 in RGCs and OLs after heat stress and/orstretch injury were observed using immunohistochemistry. Results Pathological changes of axons, RGCs and OLs after stretch injury to the optic nerves were identified morphologically or quantitatively, and significantly ameliorated by pre-treatment with heat stress before stretch injury. An increased expression of OLs HSP70 and RGCs occurred in Groups B and C. A much more enhanced expression of HSP70 was found in Group D with an earlier peak and longer maitenance period. Conclusions Both neurons and glial cells are involved in pathological process after axonal injury. Heat stress can more effectively exert the neuroprotective role through enhancing, bringing forward and prolonging expression of HSP70. A new approach to management of DAI may be developed through the enhancement of intrinsic neuroprotective functions.