HCN通道功能变化在SAH后早期脑损伤中的作用研究  

The role of HCN channels in early brain injury after SAH

作　　者：赵彤[1,2] 李博[2] 袁绍纪[2] 卢培刚[2] ZHAO Tong LI Bo YUAN Shaoji LU Peigang(Postgraduate Department of Taishan Medical University, Tai ＇an 271000 Department of Neurosurgery , General Hospital of Jinan Military Command, Jinan 250000, China)

机构地区：[1]泰山医学院研究生处,山东泰安271000 [2]济南军区总医院神经外科,山东济南250000

出　　处：《中华神经外科疾病研究杂志》2017年第2期105-109,共5页Chinese Journal of Neurosurgical Disease Research

基　　金：国家自然科学基金资助项目(81471214);济南军区总医院院长基金资助项目(2014-01)

摘　　要：目的观察大鼠模型蛛网膜下腔出血(SAH)后早期脑内超极化激活-环核昔酸门控的阳离子(HCN)通道的表达变化。评估HCN通道功能变化在SAH后早期脑损伤发生中的作用。方法动物模型的建立及分组;大鼠神经功能评价;检测神经元凋亡情况及脑脊液(CSF)中谷氨酸(Glu)含量。结果给予HCN通道阻断剂(ZD7288)后进一步加重神经功能损害及神经元凋亡,CSF中Glu含量进一步增加;而给予非特异HCN通道激动剂(NO/Sp)后并未改善神经功能损害,未能显著缓解神经元凋亡情况及降低Glu含量。结论阻断HCN通道后,神经元损伤及神经功能损害进一步加重;给予NO/Sp干预后,神经元及神经功能损害情况并未显著改善。Objective The role of hyperpolarization-activated cyclic nucleotide-gated （HCN） channels in early brain injury after subarachnoid hemorrhage （SAH） was discussed and evaluated.Methods SAH models （the arterial puncture model） in Wistar rats were established and divided into four groups with 5 rats in each including Sham group, SAH ＋ vehicle group, SAH ＋ ZD7288 group, and SAH ＋ NO/Spermine （NO/Sp） group. SAH Grading and neurological examination （Modified Garcia） were performed at 24 h after SAH in different groups. Cell death detection were performed at 24 h after SAH in different groups. Assessment of cerebrospinal fluid （CSF） and Glutamic acid （Glu） concentration were performed at 24 h after SAH in different groups. Results Inhibition of HCN channel further aggravated neurological impairment at 24 h after SAH. However unfortunately, there was no amelioration for neurological function after the treatment of NO/Sp. Neurons apoptosis in hippocampus and medial prefrontal cortex （mPFC） was observed at 24 h after SAH, especially in hippocampus. Inhibition of HCN channel by ZD7288 increased the amount of neuronal apeptosis at 24 h after SAH. However, there was no change for neuronal apoptosis between SAH and NO/Sp-treament groups. Inhibition of HCN channel by ZD7288 had a trend of increasing the Glu concentration in CSF at 24 h after SAH. Conclusion HCN channels play an important role in early brain injury after SAH. Neuronal excitability disorders caused by its function cut will directly result in the neuronal damage and eventually lead to nerve function damage after SAH. Inhibition of HCN channels will promote the vicious cycle, further aggravate the neuronal damage and neurological deficits; however, giving HCN channels nonspecific agonists does not significantly improve this （ the neuronal damage and neurological damage） situation. So this still needs further experimental research.

关 键 词：蛛网膜下腔出血 超极化激活-环核昔酸门控的阳离子通道(HCN通道) 神经元兴 奋性 神经元凋亡 早期脑损伤 

分 类 号：R651[医药卫生—外科学]