金涛 王松林 李东波 杨涛 宋锦宁

[摘要] 目的 研究弥漫性轴索损伤（DAI）对大鼠脑皮质钙释放激活钙通道调节分子1（ORAI1）表达的影响。 方法 利用瞬间旋转损伤装置，建立大鼠DAI模型，分为DAI组及对照组，DAI组又分为DAI组伤后6 h、1 d、3 d、7 d、14 d等5个亚组。运用苏木精-伊红（HE）染色观察大鼠DAI后脑皮质的病理生理变化；运用免疫组化检测大鼠脑皮质ORAI1的分布及表达。 结果 HE染色显示，DAI伤后6 h～1 d神经元变性、坏死、崩解数量增多，轴索的断裂和紊乱明显；DAI伤后3～14 d，开始恢复期改变，神经元的变性、水肿和坏死现象逐渐减少。免疫组化检测显示，与对照组比较，DAI伤后6 h大鼠脑皮质ORAI1的表达即开始增加，伤后1 d达高峰，伤后3～14 d逐渐降低，至伤后14 d时仍高于对照组（P < 0.05）。 结论 DAI后大鼠脑皮质ORAI1的表达水平呈先增加后降低的趋势，这一变化与大鼠DAI后脑皮质的病理生理变化有关，ORAI1可能参与DAI后的病理生理过程。

[关键词] 钙释放激活钙通道调节分子1；大鼠；弥漫性轴索损伤；病理生理

[中图分类号] R651.1 [文献标识码] A [文章编号] 1673-7210（2016）02（c）-0022-04

Influence of diffuse axonal injury on expression of ORAI1 in brain cortex of rat

JIN Tao1 WANG Songlin1 LI Dongbo1 YANG Tao1 SONG Jinning2

1.Department of Neurosurgery， Center Hospital of Ankang City， Shaanxi Province， Ankang 725000， China； 2.Department of Neurosurgery， the First Affiliated Hospital of Xi′an Jiaotong University， Shaanxi Province， Xi′an 710061， China

[Abstract] Objective To investigate influence of diffuse axonal injury （DAI） on expression of calcium release-activated calcium channel modulator 1 （ORAI1） in brain cortex of rat. Methods Lateral head-rotating device was used to establish DAI model. Rats were randomly divided into control group and DAI groups， which contained five subgroups （6 h， 1 d， 3 d， 7 d， 14 d after injury）. HE staining was used to observe pathological change in cerebral cortex after DAI and immunohistochemistry staining was applied to determine the distribution and expression of ORAI1. Results HE staining showed increased neuronal degeneration and necrosis at 6 h-1 d after DAI. Structural distortion of axons were observed. During 3 d to 14 d， neuronal recovery began. Degeneration， edema and necrosis of neuron gradually alleviated. Immunohistochemistry showed increase of ORAI1 expression began at 6 h in cortex after DAI； peaked at 1 d and gradually deceased from 3 d to 14 d； at 14 d， expression of ORAI1 still remained higher than control group （P < 0.05）. Conclusion ORAI1 expression significantly increase and then decrease in cerebral cortex of rats after DAI. Dynamic change of ORAI1 after DAI positively correlates with the pathological evolution， indicating the possible role of ORAI1 in pathophysiology of DAI.

[Key words] Calcium release-activated calcium channel modulator 1； Rat； Diffuse axonal injury； Pathophysiology

彌漫性轴索损伤（diffuse axonal injury，DAI）致残率及死亡率高，发病机制不清，临床尚无有效的治疗手段，深入揭示DAI的发病机制可以为临床治疗DAI提供新的思路。钙离子（Ca2+）是细胞信号传导过程中最常见的信使，在病理条件下，Ca2+超载在机体许多疾病的发生中都扮演着重要角色[1]。DAI后伴随着缺氧缺血，能量代谢发生障碍，胞内Ca2+浓度急剧升高，形成钙超载，导致钙依赖性酶激活、自由基形成、能量耗竭等一系列生化反应，最终导致细胞死亡。钙库调控的钙内流（store-operated calcium entry，SOCE）是非兴奋细胞主要的钙内流方式，参与机体众多的生理过程。SOCE的形成有两个关键蛋白，即基质相互作用分子1（stromal interaction molecule 1，STIM1）和钙释放激活钙通道调节分子1（calcium release-activated calcium channel modulator 1，ORAI1）[2]。……