盐酸右美托咪定对脑缺血再灌注损伤小鼠的保护机制  

Protective mechanism of dexmedetomidine hydrochloride on mice with cerebral ischemia-reperfusion injury

作　　者：赵海峰[1] 范鸣玥[2] 陈亮[1] 秦泽 张瑾[1] ZHAO Hai-feng;FAN Ming-yue;CHEN Liang;QIN Ze;ZHANG Jin(Department of Anesthesiology,The Fourth Hospital of Shijiazhuang,Shijiazhuang 050000,Hebei Province,China;Department of Neurology,Hebei General Hospital,Shijiazhuang 050051,Hebei Province,China)

机构地区：[1]石家庄市第四医院麻醉科,河北石家庄050000 [2]河北省人民医院神经内科,河北石家庄050051

出　　处：《中国临床药理学杂志》2021年第3期258-261,共4页The Chinese Journal of Clinical Pharmacology

基　　金：石家庄市科学技术研究与发展指导计划(第一批)基金资助项目(171461673)。

摘　　要：目的研究盐酸右美托咪定(Dex)对脑缺血/再灌注实验动物氧化应激水平的影响及初步机制。方法将108只C57小鼠随机分为假手术组、模型组和实验组,每组36只。实验组于再灌注前30 min,腹腔注射盐酸右美托咪定25μg·kg^(-1),假手术组和模型组同时间点给予等量生理盐水。用2,3,5-三苯基氯化四氮唑法(TTC)观察脑梗死组织百分比,用酶联免疫吸附(ELISA)法检测小鼠海马组织丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、过氧化氢酶(CAT)水平,用蛋白质印迹(Western blot)法检测海马组织核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)蛋白表达。结果72 h时,假手术组、模型组和实验组梗死体积百分比分别为0,(27.32±7.24)%和(8.23±3.41)%,海马组织SOD水平分别为(144.13±26.24),(49.23±15.82)和(62.37±11.92)U·mL^(-1),海马组织CAT水平分别为(68.99±13.08),(29.05±10.26)和(43.47±6.23)U·L^(-1),海马组织GSH-Px水平分别为(134.19±25.24),(51.32±13.39)和(75.29±14.32)U·L^(-1),海马组织MDA水平分别为(2.08±0.27),(5.02±0.38)和(3.48±0.29)nmol·L^(-1)。以上指标,模型组与假手术组和实验组比较,差异均有统计学意义(均P<0.05)。结论盐酸右美托咪定可通过上调Nrf2/HO-1轴,增强海马组织抗氧化活性,降低缺血/再灌注过程中氧化应激对脑组织的损伤。Objective To investigate the effect of dexmedetomidine hydrochloride(Dex)on oxidative stress level in experimental animals with cerebral ischemia/reperfusion and its preliminary mechanism.Methods A total of 108 C57 mice were randomly divided into sham operation group,model group and experimental group,36 rats in each group.Experimental group was injected with Dex 25μg·kg^(-1)intraperitoneally 30 min before reperfusion,sham operation group and model group were given the same dose of normal saline at the same time.The percentage of cerebral infarction tissues was measured by 2,3,5-triphenyl tetrazolium chloride(TTC).The levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-PX),catalase(CAT)in hippocampus of mice were detected by enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the expression of nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in hippocampus.Results At 72 h,the infarct volume percentages of sham operation group,model group and experimental group were 0,(27.32±7.24)%and(8.23±3.41)%,SOD levels in the hippocampus were(144.13±26.24),(49.23±15.82)and(62.37±11.92)U·mL^(-1),the levels of CAT in the hippocampus were(68.99±13.08),(29.05±10.26)and(43.47±6.23)U·L^(-1),the levels of GSH-Px in the hippocampus were(134.19±25.24),(51.32±13.39)and(75.29±14.32)U·L^(-1),the levels of MDA in hippocampus were(2.08±0.27),(5.02±0.38)and(3.48±0.29)nmol·L^(-1).Compared with model group,there were significant differences in the above indexes between experimental group and sham operation group(all P<0.05).Conclusion Dex can enhance the antioxidant activity of hippocampus by up-regulating Nrf2/HO-1 axis,and reduce the damage of brain tissue caused by oxidative stress during ischemia/reperfusion.

关 键 词：脑缺血/再灌注损伤 氧化应激 盐酸右美托咪定 

分 类 号：R971[医药卫生—药品]