摘要
目的研究钙池操控钙离子通道(SOCC)在蛛网膜下腔出血(SAH)后早期脑损伤中的作用,探讨SOCC与SAH后钙超载致神经元死亡的关系。方法枕大池单次注血法建立兔SAH模型,使用2-APB干扰SOCC通道活性后建立SAH干预组,Fura-2AM检测胞内钙离子浓度,Western blotting检测SOCC通道蛋白STIM1和ORAI1的表达变化,并与正常对照组、假手术组相比较,TUNEL检测皮层神经元凋亡。结果 SAH后皮层中STIM1和ORAI1蛋白表达均持续升高,在3d时达到高峰,同时皮层神经元胞内钙离子浓度达到峰值。给予SOCC通道阻断剂后,皮层STIM1和ORAI1蛋白表达被抑制,皮层神经元钙内流减低,神经功能评分改善。结论 SAH后神经元的钙超载是造成早期脑损伤的重要原因;抑制SOCC产生的钙内流可缓解神经细胞死亡,改善神经功能。
Objective To investigate the possible role of store-operated calcium channels (SOCC) in early brain injury (EBI) after subarachnoid hemorrhage (SAH) and to explore the relationship between SOCC and calcium overload induced delayed neuronal death (DND) after SAH. Methods Rabbits models of SAH were established using the single-blood injection method via the cisterna magna. SAH intervention group was established by intracerebroventricular injection of 2-aminoethyldiphenyl borate (2-APB). lntracellular calcium concentration was detected by Fura-2AM. The dynamic expression of SOCC was determined by Western blot. The apoptosis of cortical neurons was detected by TUNEL. One-way ANOVA was used to compare between experimental, normal control and sham-operation groups. Results The protein expressions of STIM1 and ORAI1 in the cortex increased continuously after SAH and reached the peak at day 3; intracellular calcium concentration also reached the peak. After injection of SOCC blocker, the protein expressions of STIM1 and ORAI1 were inhibited and intracellular calcium concentration decreased. Meanwhile, the scores of neurological functions in rabbits were improved. Oonclusion Calcium overload in neurons after SAH plays a key role in EBI. Suppressing the calcium influx induced by SOCC could delay neuronal death and improve neurological functions.
出处
《西安交通大学学报(医学版)》
CAS
CSCD
北大核心
2013年第6期710-716,共7页
Journal of Xi’an Jiaotong University(Medical Sciences)
基金
国家自然科学基金资助项目(No.30870844)
陕西省"13115"重大科技创新专项基金资助项目(No.2008ZDKG-66)
教育部高等学校博士学科点专项科研基金资助项目(No.20110201110060)~~
关键词
蛛网膜下腔出血
早期脑损伤
SOCC
STIM1
ORAI1
细胞凋亡
兔
subarachnoid hemorrhage (SAH)
early brain injury
store-operated calcium channel (SOCC)
STIM1
ORAI1
apoptosis
rabbits