反义p53对创伤后神经元的保护作用

目的 观察p53反义寡核苷酸对创伤后迟发性神经元死亡的防治效果。方法在自由落体打击大鼠弥漫性脑创伤模型中,转染反义寡核苷酸药物,以大鼠神经功能行为评分及Tunel法检测鼠脑皮层神经元DNA损伤情况作为疗效评价指标;用原位杂交、免疫组化法检测p53 mRNA与蛋白质的表达水平。结果大鼠打击后,神经功能行为评分下降,皮层打击区伤后1周内出现神经元凋亡现象。脑创伤后2～4h p53 mRNA及蛋白表达增加。p53反义寡核苷酸转染后的大鼠,神经功能评分明显改善;神经元凋亡数量明显减少;p53 mRNA及蛋白表达减少。结论细胞凋亡在创伤性脑损伤中起重要作用,对创伤后神经功能的缺损有重要影响;反义p53抑制脑创伤后细胞凋亡的发生可能成为治疗创伤性脑损伤后迟发性神经元死亡的新途径。

The protective effect of p53 antisense oligonucleotide against neuron apoptosis secondary to traumatic brain injury

Objective To observe the phenomenon of delayed neuron death secondary to traumatic brain injury,and the protective effect of p53 antisense oligonucleotide against neuron apoptosis secondary to traumatic brain injury Methods This study was based on the rat diffuse brain trauma model established by a simple weight drop device The behavior scales of neural function of rats and Tunel that examined the injury extent of DNA in the cortex were used as a general assessment of brain injury Electrical microscope was used to observe the histological and cellular morphology mRNA and protein expression of p53 were detected by in situ hybridization and immunohistochemistry In this model,the therapeutic effect of p53 antisense drug were observed Results Following trauma,the behavior scores of rats decreased rapidly and remarkably Apoptotic neurons appeared in the traumatized cortex as early as 2 hours after impact,and peaked at 24 hours As early as 2 hours after impact,p53 mRNA and p53 protein in the cortex were expressed increasingly Conclusion Neural apoptosis plays an important role in delayed neuron death and is responsible for neural dysfunction following traumatic brain injury So the inhibition of neural apoptisis would turn into a new therapic measure against delayed neuron death following traumatic brain injury