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咪达唑仑减轻脑缺血/再灌注模型大鼠脑损伤OA

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

中文摘要英文摘要

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.

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(intra-peritoneal 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 apopto-sis,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 neurolog-ical 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 par-tially activate the Hippo/YAP signaling pathway and reduce brain tissue damage.

左勇;司玉婷;王洋;赵晓亮

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

医药卫生

咪达唑仑Hippo/Yes相关蛋白质(YAP)脑缺血/再灌注脑保护

midazolamHippo/Yes-associated protein(YAP)cerebral ischemia-reperfusioncerebral protection

《基础医学与临床》 2026 (9)

1237-1242,6

新疆维吾尔自治区科技计划(2024D01C287)

10.16352/j.issn.1001-6325.2026.09.1237

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