PTSD样大鼠杏仁核内质网分子伴侣GRP 94和caspase-12表达的改变

The expression changes of the endoplasmic reticulum molecular chaperone glucose regulated protein 94 and caspase-12 in the amygdala of posttraumatic stress disorder rats

目的探讨杏仁核神经元内质网应激(ERS)相关因子葡萄糖调节蛋白94(GRP94)及胱冬酶12(c)在创伤后应激障碍(PTSD)大鼠发生发展中的作用。方法建立无连续单一刺激(SPS)模型,随机分为SPS刺激后7天组(SPS7d)、14天组(SPS14d)及正常对照组。应用免疫组织化学、Western Blot、RT-PCR和透射电镜技术,检测和观察各组杏仁核神经元GRP94、caspase12 mRNA与蛋白表达及超微结构变化。结果与正常对照组相比,SPS7d组和SPS14d组神经元GRP94蛋白表达水平明显增加,GRP94 mRNA和caspase-12 mRNA表达水平也明显增加(P<0.05);SPS各组神经元均有核内异染色质凝聚、边集及粗面内质网扩张等不同程度的改变。结论 SPS刺激可能通过杏仁核神经元GRP94表达增加启动了内质网自稳调节系统及内质网相关的caspase-12凋亡径路,进而参与PTSD的发生。

Objective To observe the expression changes of glucose regulated protein 94 and caspase 12 in the amygdala of posttraumatic stress disorder rat. Methods The rats were randomly assigned to： normal control, SPS groups（single-prolonged stress model, 7d,14d）. The expression of GRP94 and GRP94 mRNA and caspasel2 mRNA were examined by immunohistochemistry and Western blotting and RT-PCR respectively, the ultrastructure of amygdala was observed by transmission electron microscope. Results Compared to the normal control, the expression level of GRP94 protein in amygdala was increased in both SPS7d and SPS14d groups（P〈0.05）, the expression levels of GRP94 mRNA and caspasel2 mRNA in amygdala were also upregulated significantly in both SPS7d and SPS14d groups（P〈0.05）, with different ultrastucture changes of heteroehromatin condensation, aggregated peripherally and the dilation of rough endoplasmic reticulum in amygdaloid nucleus of SPS group. Conclusion The overexpression of GRP94 and caspsae-12 in amygdala might be related to the pathogenesis of PTSD.