格列美脲通过抑制SUR1-TRPM4通道减轻蛛网膜下腔出血大鼠脑水肿和凋亡  

Glimepiride alleviates cerebral edema and apoptosis in rats with subarachnoid hemorrhage by inhibiting SUR1-TRPM4 channel

作　　者：郝广志 董雨佳 郇宇 董玉书 HAO Guangzhi;DONG Yujia;HUAN Yu;DONG Yushu(Department of Neurosurgery,General Hospital of Northern Theater Command,Shenyang 110016;Bachelor of Anesthesiology,Class 2022,Chifeng Clinical Medical College,Inner Mongolia Medical University,Hohhot 010100,China)

机构地区：[1]中国人民解放军北部战区总医院神经外科,沈阳110016 [2]内蒙古医科大学赤峰临床医学院,呼和浩特010100

出　　处：《神经解剖学杂志》2025年第1期67-72,共6页Chinese Journal of Neuroanatomy

基　　金：辽宁省科技计划联合计划(2024JH2/102600282)。

摘　　要：目的:探讨格列美脲对蛛网膜下腔出血(SAH)脑水肿和细胞凋亡的影响。方法:利用颈内动脉穿刺法制备大鼠SAH模型,腹腔注射法给予格列美脲进行治疗,通过改良神经功能缺损评分(mNSS)方法进行神经功能缺损评分,通过大鼠脑组织的干湿比评估大鼠含水量。利用RT-qPCR检测大鼠脑组织中SUR1和TRPM4 mRNA的表达,Western blot检测脑组织中Bcl-2和Bax的表达。结果:SAH大鼠神经功能受损,脑含水量增加,同时SUR1和TRPM4 mRNA表达上调,Bcl-2/Bax比值下降。低剂量的格列美脲不影响大鼠血糖浓度,但是可以显著改善SAH大鼠神经功能,减轻脑水肿;虽然格列美脲对SUR1和TRPM4 mRNA表达没有显著影响,但能够增加Bcl-2/Bax比值。结论:格列美脲通过抑制SUR1-TRPM4通道减轻SAH模型大鼠脑水肿,并抑制细胞凋亡。Objective:To investigate the effects of glimepiride on cerebral edema and apoptosis in a rat model of subarachnoid hemorrhage(SAH).Methods:An SAH model was established in rats using the internal carotid artery puncture method.Low-dose glimepiride was administered via intraperitoneal injection.Neurological deficits were assessed using the modified Neurological Severity Score(mNSS),and brain water content was evaluated by measuring the wet-dry weight ratio of brain tissue.Cortical tissue from the surgical side was collected to measure the mRNA expression of sulfonylurea receptor 1(SUR1)and transient receptor potential melastatin 4(TRPM4)using RT-qPCR,while the protein expression of Bcl-2 and Bax was detected by Western blot.Results:SAH rats exhibited impaired neurological function,increased brain water content,upregulation of SUR1 and TRPM4 mRNA expression,and a decreased Bcl-2/Bax ratio.Low-dose glimepiride did not affect blood glucose levels but significantly improved neurological function and reduced cerebral edema in SAH rats.Although glimepiride had no significant effect on SUR1 and TRPM4 mRNA expression,it increased the Bcl-2/Bax ratio.Conclusion:Glimepiride alleviates cerebral edema and inhibits apoptosis in SAH model rats by suppressing the SUR1-TRPM4 channel.

关 键 词：磺酰脲类药物受体1(SUR1) 瞬时受体电位4(TRPM4) 脑水肿 早期脑损伤 蛛网膜下腔出血 大鼠 

分 类 号：R74[医药卫生—神经病学与精神病学]