咪达唑仑减轻脑缺血/再灌注模型大鼠脑损伤

doi:10.16352/j.issn.1001-6325.2026.09.1237

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (9): 1237-1242.doi: 10.16352/j.issn.1001-6325.2026.09.1237

咪达唑仑减轻脑缺血/再灌注模型大鼠脑损伤

左勇¹, 司玉婷², 王洋², 赵晓亮^1*

1.新疆维吾尔自治区人民医院白鸟湖医院(西安交通大学第二附属医院新疆医院)麻醉手术中心,新疆乌鲁木齐 830032;
2.新疆维吾尔自治区人民医院麻醉手术中心新疆麻醉管理临床医学研究中心,新疆乌鲁木齐 830001

收稿日期:2025-06-30 修回日期:2025-10-17 出版日期:2026-09-05 发布日期:2026-08-18
通讯作者: ^*24653127@qq.com
基金资助:
新疆维吾尔自治区科技计划(2024D01C287)

Midazolam alleviates brain injury in rat models caused by cerebral ischemia-reperfusion

ZUO Yong¹, SI Yuting², WANG Yang², ZHAO Xiaoliang^1*

1. Anesthesia and Surgery Center, Bainiaohu Hospital (Xinjiang Hospital of Xi′an Jiaotong University Second Affiliated Hospital), Xinjiang Uygur Autonomous Region People′s Hospital, Urumqi 830032;
2. Anesthesia and Surgery Center, Xinjiang Anesthesia Management Clinical Medical Research Center, Xinjiang Uygur Autonomous Region People′s Hospital, Urumqi 830001, China

Received:2025-06-30 Revised:2025-10-17 Online:2026-09-05 Published:2026-08-18
Contact: ^*24653127@qq.com

摘要/Abstract

摘要： 目的探讨咪达唑仑(MDZ)对脑缺血/再灌注损伤(CI/RI)大鼠脑损伤的影响。方法将CI/RI模型大鼠分为CI/RI组、MDZ-L组、MDZ-M组和MDZ-H组(经颈静脉注射0.05、0.15、0.30 mg/kg的MDZ)、MDZ-H+verteporfin(Hippo/YAP信号通路抑制剂)组(腹腔注射10 mg/kg verteporfin)。对照(control)组与CI/RI组给予等量0.9%氯化钠溶液。记录大鼠神经功能缺损评分;氯化三苯基四氮唑(TTC)法观察大鼠脑梗死面积;HE染色、TUNEL染色分别观察脑组织病理变化、神经元凋亡情况;ELISA检测大鼠脑组织中炎性因子水平;Western blot检测大鼠脑组织中Hippo/YAP信号通路蛋白质表达。结果 CI/RI组较对照组大鼠脑组织神经细胞排列疏松,细胞体积增大,细胞核偏移;MDZ-L组、MDZ-M组、MDZ-H组较CI/RI组大鼠脑组织损伤减轻;MDZ-H+verteporfin组较MDZ-H组大鼠脑组织损伤加重。CI/RI组较对照组大鼠神经功能缺损评分、脑梗死面积、脑组织中TNF-α、IL-1β水平、神经元凋亡率升高,脑组织中YAP、TAZ蛋白表达降低(P＜0.05);MDZ-L、MDZ-M和MDZ-H组较CI/RI组大鼠神经功能缺损评分、脑梗死面积、脑组织中TNF-α、IL-1β水平、神经元凋亡率降低,脑组织中YAP、TAZ蛋白表达升高(P＜0.05);MDZ-H+verteporfin组以上指标均发生了逆转(P＜0.05)。结论 MDZ能部分激活Hippo/YAP信号通路,减少脑组织损伤。

关键词: 咪达唑仑, Hippo/Yes相关蛋白质(YAP), 脑缺血/再灌注, 脑保护

Abstract: Objective To investigate the effect of midazolam (MDZ) on brain injury in rats with cerebral ischemia-reperfusion injury(CI/RI). Methods Rats with CI/RI were divided into five groups: CI/RI group, MDZ-L group (intravenous injection of 0.05 mg/kg MDZ), MDZ-M group (0.15 mg/kg MDZ) and MDZ-H group (0.30 mg/kg MDZ). Additionally, there was an MDZ-H + verteporfin(inhibitor of Hippo/YAP signaling pathway) group (intraperitoneal injection of 10 mg/kg verteporfin). The control group received an equivalent volume of saline.Outcomes were evaluated by neurological deficits,infarct volume, histopathological changes in brain tissue, neuronal apoptosis, inflammatory cytokines and related protein expression. Results The CI/RI group showed loosening of neuronal arrangement, enlarged cell bodies, and nuclear shift as compared to the control group. The brain tissue damage was less severe in the MDZ-L, MDZ-M, and MDZ-H groups as compared to the CI/RI group. The MDZ-H + verteporfin group exhibited more severe brain tissue damage than the MDZ-H group. The CI/RI group showed increased neurological deficit scores, infarct volume, level of TNF-α and IL-1β in brain tissue, and neuronal apoptosis rate as compared to the control group, while the expression of YAP and TAZ proteins in brain tissue was decreased (P＜0.05). The MDZ-L, MDZ-M, and MDZ-H groups showed a decrease in neurological deficits, infarct size, inflammatory cytokines and apoptosis rate, along with increased YAP and TAZ protein expression compared to the CI/RI group (P＜0.05). The MDZ-H + verteporfin group showed a reversal picture of these indicators (P＜0.05). Conclusions MDZ can partially activate the Hippo/YAP signaling pathway and reduce brain tissue damage.

Key words: midazolam, Hippo/Yes-associated protein(YAP), cerebral ischemia-reperfusion, cerebral protection

中图分类号:

R614

左勇, 司玉婷, 王洋, 赵晓亮. 咪达唑仑减轻脑缺血/再灌注模型大鼠脑损伤[J]. 基础医学与临床, 2026, 46(9): 1237-1242.

ZUO Yong, SI Yuting, WANG Yang, ZHAO Xiaoliang. Midazolam alleviates brain injury in rat models caused by cerebral ischemia-reperfusion[J]. Basic & Clinical Medicine, 2026, 46(9): 1237-1242.

参考文献

[1] Campbell BCV, Khatri P. Stroke[J]. Lancet, 2020, 396(10244):129-142.
[2] Liu Y, Wang W, Di B, et al. Curcumol ameliorates neuroinflammation after cerebral ischemia-reperfusion injury via affecting microglial polarization and Treg/Th17 balance through Nrf2/HO-1 and NF-κB signaling[J]. Cell Death Discov, 2024, 10:300-313.
[3] Terry BK, Kim S. The role of Hippo/YAP/TAZ signaling in brain development[J]. Dev Dyn, 2022, 251:1644-1665.
[4] Antón IM, Wandosell F. WIP, YAP/TAZ and actin connections orchestrate development and transformation in the central nervous system[J]. Front Cell Dev Biol, 2021, 9:1-9.
[5] Conway A, Chang K, Mafeld S, et al. Midazolam for sedation before procedures in adults and children: a systematic review update[J]. Syst Rev, 2021, 10:69-81.
[6] Soyalp C, Oksuz E, Gorgisen G, et al. Role of sedative-hypnotic agents in neurodegeneration: effects of mida-zolam and thiopental on apoptosis and oxidative stress expression in neonatal and adult rat brains[J]. Turk Neurosurg, 2022, 32:378-385.
[7] Xu S, Huang P, Yang J, et al. Calycosin alleviates cerebral ischemia/reperfusion injury by repressing autophagy via STAT3/FOXO3a signaling pathway[J]. Phytomedicine, 2023, 115:43-56.
[8] 孟元元, 刘艳, 张华强, 等. 静脉注射咪达唑仑对蛛网膜下腔出血大鼠脑神经炎性和损伤的改善作用及其机制[J]. 山东医药, 2023, 63:26-30.
[9] Huang L, Li S, Dai Q, et al. Astrocytic Yes-associated protein attenuates cerebral ischemia-induced brain injury by regulating signal transducer and activator of transcrip-tion 3 signaling[J]. Exp Neurol, 2020, 333:27-34.
[10] 彭莹娟, 李志营, 孙林林, 等. 赤芍总苷减轻脑缺血/再灌注模型大鼠脑损伤[J]. 基础医学与临床, 2025, 45:25-30.
[11] Wang S, Shi X, Xiong T, et al. Inhibiting mitochondrial damage for efficient treatment of cerebral ischemia-reperfusion injury through sequential targeting nanomedicine of neuronal mitochondria in affected brain tissue[J]. Adv Mater, 2024, 36:1-12.
[12] Riva A, Iapadre G, Grasso EA, et al. Intramuscular midazolam for treatment of status epilepticus[J]. Expert Opin Pharmacother, 2021, 22:37-44.
[13] Jin J, Zhao X, Fu H, et al. The effects of YAP and its related mechanisms in central nervous system diseases[J]. Front Neurosci, 2020, 14:595-609.
[14] Hong J, Kirkland JM, Acheta J, et al. YAP and TAZ regulate remyelination in the central nervous system[J]. Glia, 2024, 72:156-166.
[15] 张雪梅, 邬合旭, 袁雄. 西格列汀调节Hippo/YAP信号通路对脑出血大鼠脑组织损伤的影响[J]. 卒中与神经疾病, 2025, 32:46-50+69.

咪达唑仑减轻脑缺血/再灌注模型大鼠脑损伤

Midazolam alleviates brain injury in rat models caused by cerebral ischemia-reperfusion

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 14

编辑推荐

Metrics

本文评价

[1]	杨春晖, 肖婷, 刘华, 杨坤渹. 咪达唑仑减轻碘乙酸钠诱导的骨关节炎模型大鼠软骨损伤和疼痛[J]. 基础医学与临床, 2026, 46(9): 1243-1248.
[2]	徐伯鑫, 山媛, 杨云鹏. D-松醇缓解脑缺血/再灌注模型大鼠的脑损伤[J]. 基础医学与临床, 2026, 46(3): 359-366.
[3]	杨溢伟, 孙晓伟. 治疗脑缺血/再灌注损伤中NLRP3炎性小体介导的细胞焦亡的研究进展[J]. 基础医学与临床, 2026, 46(3): 435-439.
[4]	夏洪莲, 张艳丽, 钟微微, 刘永梁, 陈猛, 崔红蕾. 异丙酚预处理减轻大鼠局灶性脑缺血再灌注损伤[J]. 基础医学与临床, 2026, 46(2): 227-232.
[5]	赵海燕, 王怡洁, 刘荣, 杨吉林, 李婷, 朱晓琳, 秦佳宏. 大鼠脑组织sigma-1受体表达与心肺复苏后脑损伤相关[J]. 基础医学与临床, 2025, 45(9): 1200-1207.
[6]	彭莹娟, 李志营, 孙林林, 杨会杰, 王甜甜, 周丽平. 赤芍总苷减轻脑缺血/再灌注模型大鼠脑损伤[J]. 基础医学与临床, 2025, 45(1): 25-30.
[7]	陈涛, 陈凌君, 李媛. 咪达唑仑减轻氧糖剥夺/复糖复氧诱导的小鼠神经元损伤[J]. 基础医学与临床, 2024, 44(4): 459-466.
[8]	魏健强, 张春瑞. 咪达唑仑减轻缺氧/复氧诱导的小鼠海马神经元损伤[J]. 基础医学与临床, 2023, 43(2): 252-258.
[9]	陈宁宁, 应新旺, 谢庆凤. 抑制小凹蛋白减轻大鼠脑缺血/再灌注诱导的神经功能损伤[J]. 基础医学与临床, 2022, 42(12): 1879-1884.
[10]	姚霞张明. 整合素α5β1与缺血性卒中的研究进展[J]. 基础医学与临床, 2013, 33(12): 1630-1633.
[11]	杜建丽梁婧李沫音张旭赵丽罗艳琳李俊发. MSK-1和CREB参与低氧预适应降低小鼠缺血性脑损伤[J]. 基础医学与临床, 2010, 30(11): 1143-1148.
[12]	罗琼袁恒杰吴艳娜康毅高卫真刘艳霞娄建石. 无创性延迟肢体缺血预适应减轻大鼠脑缺血/再灌注损伤[J]. 基础医学与临床, 2009, 29(6): 603-606.
[13]	张高峰李刚许永光. 丙泊酚联合不同剂量咪达唑仑在长时间显微外科手术患者中的镇静[J]. 基础医学与临床, 2008, 28(7): 774-777.
[14]	杨冀萍刘怀军李英刘燕李春岩. NGF对兔脑缺血／再灌注损伤半胱氨酸蛋白酶-12的影响[J]. 基础医学与临床, 2007, 27(4): 408-411.