咪哒唑仑对新生大鼠缺氧缺血性脑损伤的神经保护作用  

Neuroprotective Effect of Midazolam on Hypoxic-ischemic Brain Damage in Neonatal Rats

作　　者：俞立奇 界中平 桑征 张雪松[1] YU Liqi;JIE Zhongping;SANG Zheng;ZHANG Xuesong(Department of Anesthesiology,Shanghai Public Health Clinical Center,Shanghai,201508,China)

机构地区：[1]上海市公共卫生临床中心麻醉科,上海市201508

出　　处：《医学分子生物学杂志》2021年第2期77-82,共6页Journal of Medical Molecular Biology

基　　金：上海市公共卫生临床中心临床科研项目(No.KY-GW-2019-28)。

摘　　要：目的 探究咪达唑仑(midazolam,Mida)对新生大鼠缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)神经的保护作用.方法 建立HIBD新生大鼠模型,Mida处理后,行为实验评估大鼠的神经功能;2,3,5-三苯基四氮唑(TTC)检测大鼠脑梗死率,测量大鼠脑含水率和脑指数;苏木精-伊红(HE)和尼氏染色检测病理损伤;TUNEL检测神经细胞凋亡,Western印迹检测脑组织活化胱天蛋白酶(cleaved caspase)-3,cleaved cas-9、B细胞淋巴瘤(Bcl)-2和B细胞淋巴瘤2相关的X蛋白(Bax)的表达;试剂盒测定血清超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)和乳酸脱氢酶(lactic dehydrogenase,LDH)含量;ELISA检测大鼠血清中炎性因子水平.结果 Mida能明显改善HIBD大鼠的神经行为功能障碍,减轻脑梗死率和脑水肿(P<0.05);有效缓解造模诱导的病理损伤;减少脑组织细胞凋亡率,下调凋亡蛋白表达(P<0.05);提高HIBD大鼠抗氧化能力,降低诱导型一氧化氮合酶(iNOS)和白细胞介素(IL)-1β水平,升高IL-10水平(P<0.05).结论 Mida抑制HIBD诱导的脑组织凋亡,氧化应激和炎性反应,对HIBD大鼠具有神经保护作用.Objective To explore the neuroprotective effect of midazolam(Mida)on hypoxicischemic brain damage(HIBD)in neonatal rats.Methods The neonatal rat model of HIBD was established.After Mida treatment,the neurological function of the rats was evaluated by behavioral experiment.2,3,5-triphenyltetrazolium(TTC)was used to detect the cerebral infarction rate of the rats,and the brain water content and brain index of rats were measured.Pathological damage was detected by hematoxylin-eosin(HE)and Nissl staining.TUNEL was employed to detect neuronal apoptosis.Western blotting was performed to detect the expression of cleaved caspase-3,cleaved cas-9,B cells lymphoma(Bcl)-2 and B cell lymphoma 2 related X protein(Bax)of brain tissue.The content of superoxide dismutase(SOD),malondialdehyde(MDA)and lactic dehydrogenase(LDH)in serum was measured by the kit.The level of inflammatory factors in rat serum was detected by ELISA.Results Mida significantly improved the neurobehavioral dysfunction of HIBD rats,reduced the rate of cerebral infarction and cerebral edema,effectively alleviated the pathological damage induced by modeling,reduced the apoptosis rate of brain tissue and down-regulated the expression of apoptotic protein(P<0.05),improved the antioxidant capacity of HIBD rats,reduced the levels of inducible nitric oxide synthase(iNOS)and interleukin(IL)-1β,and increased the level of IL-10(P<0.05).Conclusion Mida inhibits brain tissue apoptosis,oxidative stress and inflammation induced by HIBD,and has neuroprotective effects on HIBD rats.

关 键 词：缺氧缺血性脑损伤 咪达唑仑 细胞凋亡 氧化应激 炎性反应 

分 类 号：R748[医药卫生—神经病学与精神病学]