甲基强的松龙对大鼠脊髓损伤后细胞凋亡的影响

目的 观察大剂量甲基强的松龙（methylprednisolone,MP）对大鼠脊髓损伤（spinal cord injury,SCI）后神经细胞凋亡及凋亡相关基因表达的影响.方法 72只健康雌性Wistar大鼠随机分为创伤对照组及MP治疗组,各36只.以Allen′s法制作大鼠SCI模型.MP的给药方法为术后30 min内经鼠尾静脉给予MP 30 mg/kg;创伤对照组给予等容积生理盐水.术后1 h、4 h、12 h、24 h、3 天、7 天处死动物,取出脊髓组织,TUNEL检测细胞凋亡,逆转录-聚合酶链反应（RT-PCR）法检测Bcl-2、Bax mRNA.结果 SCI 24 h时,脊髓组织细胞凋亡达高峰,然后逐渐下降,给予MP治疗后,与创伤对照组比较凋亡指数明显降低（P＜0.05或P＜0.01）.Bcl-2、Bax mRNA结果显示,在SCI 4 h后各时间点MP组大鼠Bcl-2/Bax比值高于创伤对照组,24 h时更明显（P＜0.05或P＜0.01）.结论 细胞凋亡是SCI早期主要的生物学事件;细胞凋亡的调控基因家族Bcl-2/Bax通过调节细胞凋亡参与SCI的发生发展;MP可抑制大鼠SCI细胞的凋亡,从而实现对SCI的影响.

Effect of methylprednisolone on cell apoptosis following spinal cord injury in rats

Objective To investigate the effect of high dose of methylprednisolone （MP） on neuron apoptosis and the expression of apoptosis - related genes following spinal cord injury （SCI） in rats. Methods 72 healthy female Wistar rats were randomized into trauma control group and MP treatment group （u = 36 each）. Allen＇ s method was used to establish rat SCI model. MP was given via the vena caudalis at a dose of 30 mg/kg within 30 rain after the operation, while the control group was injected with the same dose of normal saline. 1 h, 4 h, 12 h, 24 h, 3 d and 7 d postoperatively, the rats were sacrificed and the spinal cord including the injured site were obtained. The terminal deoxynueleotide transferasemediated DUTP- biotin nick end labeling （TUNEL） was used to observe neural apoptosis; RT- PCR was used to determine the expressions of Bcl - 2 and Bax mRNA in different groups. Results The apoptosis of the spinal tissue reached its peal 24 h after SCI and then began to decline. Following MP treatment, the apoptotic index markedly decreased and there was significant difference compared with the trauma control group （P 〈 0.05 or P 〈 0.01 ）. The resuits of image analysis of Bcl - 2 and Bax mRNA showed that the ratio of Bcl - 2/Bax of MP group higher than that in the trauma control group （ P 〈 0.05 or P 〈 0.01 ）. Conclusion Apoptosis is an important biological event of early SCI ; Bcl -2/Bax, gene family regulating cell apoptosis, participate in the pathogenesis and progression of SCI via tile regulation of the process of apoptosis. MP can inhibit the SCI - induced apoptosis induced in rats.