右美托咪定对缺氧缺血新生大鼠脑损伤的保护作用  

Protective Effect of Dexmedetomidine on Brain Injury in Neonatal Rats with Hypoxia-ischemia

作　　者：郑思敏 王倩茹[1] 牛晓丽[1] Zheng Simin;Wang Qianru;Niu Xiaoli(The Second Affiliated Hospital of Xi'an Jiaotong University,Xian,710061)

机构地区：[1]西安交通大学第二附属医院,西安710061

出　　处：《基因组学与应用生物学》2020年第10期4746-4752,共7页Genomics and Applied Biology

摘　　要：为了揭示右美托咪定后处理对缺氧缺血(HI)新生大鼠脑损伤的保护作用本研究将80只7日龄SD大鼠随机分为4组(n=20),分别为Sham组、HI组、HI+Dex组和HI+Dex+Yoh组。HI+Dex组大鼠在脑缺氧缺血1 h后腹膜内注射10μg/kg右美托咪定;HI+Dex+Yoh组大鼠腹膜内注射10μg/kg右美托咪定和5 mg/kg育亨宾。脑缺氧缺血24 h后处死一部分大鼠并收集脑组织用于后续指标检测;另一部大鼠继续用药6d,间隔2周后即30日龄时进行神经功能缺损评分的评估及水迷宫实验。大鼠治疗2周后的神经功能缺损评分显示,HI+Dex组的神经功能缺损评分显著低于HI组。在Morris水迷宫实验中,定位航行实验和空间探索实验显示,HI+Dex组的逃避潜伏期显著低于HI组,而穿越平台次数显著高于HI组。海马的TUNEL染色显示,HI+Dex组的TUNEL阳性细胞率显著低于HI组。RT-PCR和免疫组织化学染色显示,HI+Dex组大鼠海马组织AQP4、MMP9和ApoJ的表达水平显著低于HI组。Western blotting结果显示,HI+Dex组大鼠海马组织PI3K、AKT和GSK-3β的磷酸化水平显著高于HI组;此外,HI+Dex组大鼠皮质组织中TNF-α和IL-1β含量显著低于HI组。本研究表明右美托咪定后处理可通过激活α2AR对脑缺氧缺血新生大鼠提供脑保护作用。To reveal the protective effect of dexmedetomidine post-treatment on brain injury in neonatal rats with hypoxia-ischemia(HI).Eighty 7-day-old SD rats were randomly divided into 4 groups(n=20),which were Sham group,HI group,HI+Dex group and HI+Dex+Yoh group.Rats in the HI+Dex group were injected intraperitoneally with 10μg/kg dexmedetomidine 1 h after cerebral hypoxia-ischemia,and rats in the HI+Dex+Yoh group were injected intraperitoneally with 10μg/kg dexmedetomidine and 5 mg/kg yohimbine.After 24 h of cerebral hypoxia-ischemia,a portion of the rats were sacrificed and brain tissue was collected for subsequent index detection.Another rat continued to take the drug for 6 days,and after 2 weeks interval,that is,at 30 days of age,the neurological deficit score evaluation and water maze experiment were performed.The neurological deficit score in rats after 2 weeks of treatment showed that the neurological deficit score of HI+Dex group was significantly lower than that of the HI group.In the Morris water maze experiment,location navigation experiments and space exploration experiments showed that the escape latency of the HI+Dex group was significantly lower than that of HI group,while the number of crossing platforms was significantly higher than that of HI group.TUNEL staining of hippocampal showed that the rate of TUNEL-positive cells in HI+Dex group was significantly lower than that in HI group.RT-PCR and immunohistochemical staining showed that the expression levels of AQP4,MMP9 and ApoJ in hippocampus of rats in HI+Dex group were significantly lower than those in HI group.Western blotting results showed that the levels of PI3 K,AKT and GSK-3βin hippocampus of HI+Dex group were significantly higher than those in HI group.In addition,the levels of TNF-αand IL-1βin the cortex of HI+Dex group were significantly lower than those in HI group.This study shows that dexmedetomidine post-treatment can provide cerebral protection for neonatal rats with cerebral hypoxia-ischemia by activatingα2 AR.

关 键 词：右美托咪定 脑缺氧缺血 细胞凋亡 脑损伤 

分 类 号：R614[医药卫生—麻醉学]