右美托咪定对颅脑损伤大鼠海马神经细胞凋亡及Omi/HtrA2信号通路的影响  

Effects of Dexmedetomidine on Hippocampal Neuron Apoptosis and Omi/HtrA2 Signaling Pathway in Rats with Craniocerebral Injury

作　　者：张琦 吴军 郭阳 谷月舜 ZHANG Qi;WU Jun;GUO Yang;GU Yue-shun(Department of Anesthesiology,Yanggu County People’s Hospital,Yanggu 252300,China;Department of General Surgery,Yanggu County People’s Hospital,Yanggu 252300,China;Department of Neurology,Liaocheng People’s Hospital,Liaocheng 252000,China)

机构地区：[1]阳谷县人民医院麻醉科,山东阳谷252300 [2]阳谷县人民医院普外科,山东阳谷252300 [3]聊城市人民医院神经内科,山东聊城252000

出　　处：《南昌大学学报（医学版）》2021年第2期18-22,28,共6页Journal of Nanchang University：Medical Sciences

摘　　要：目的探究右美托咪定(DEX)对颅脑损伤大鼠海马神经细胞凋亡及Omi/HtrA2信号通路的影响。方法采用随机数字表法将60只雄性SD大鼠分为:假手术组、颅脑损伤组、低剂量和高剂量DEX组,每组15只。除假手术组外,其余3组均采用自由落体法建立大鼠颅脑损伤模型。低剂量和高剂量DEX组分别腹腔注射25和50μg·kg-1 DEX,假手术组和颅脑损伤组腹腔注射等量生理盐水。Longa法评价大鼠神经功能损伤;Y迷宫实验检测大鼠脑认知功能(逃离时间、错误反应次数);TUNEL法检测各组海马组织神经细胞凋亡;蛋白质印迹实验检测各组X染色体连锁凋亡抑制蛋白(XIAP)、Omi/HtrA2蛋白表达、聚腺苷二磷酸-核糖多聚蛋白(PRAP)、pro-Caspase-3、pro-Caspase-9、Caspase-3、Caspase-9蛋白表达水平;HE染色观察大鼠海马区病理学变化。结果与假手术组比较,颅脑损伤组大鼠逃离时间、错误反应次数、神经功能评分、神经细胞凋亡率及PRAP、Omi/HtrA2、Caspase-3、Caspase-9、pro-Caspase-3和pro-Caspase-9蛋白相对表达均显著升高(均P<0.05),XIAP蛋白相对表达量显著降低(P<0.05),且海马区神经细胞分布散乱,伴有大量神经细胞的缺失和坏死。与颅脑损伤组比较,DEX组大鼠逃离时间、错误反应次数、神经功能评分、神经细胞凋亡率及PRAP,Omi/HtrA2,Caspase-3,Caspase-9,pro-Caspase-3和pro-Caspase-9蛋白相对表达均显著降低(均P<0.05),XIAP蛋白相对表达量显著升高(P<0.05),海马区神经细胞缺失和坏死显著减少,细胞排列较为均匀;而且,高剂量DEX组的效果均优于低剂量组。结论DEX可抑制颅脑损伤大鼠海马神经细胞的凋亡,这可能与其抑制Omi/HtrA2通路及凋亡相关蛋白的表达有关。Objective To explore the effects of dexmedetomidine(DEX)on hippocampal neuron apoptosis and Omi/HtrA2 signaling pathway in rats with craniocerebral injury.Methods Sixty male SD rats were randomly divided into four groups,with 15 rats in each group.Craniocerebral injury model was established using the free fall method.The low-dose and high-dose DEX groups were intraperitoneally injected with 25 and 50μg·kg-1 DEX,respectively.The sham operation group and craniocerebral injury group were given the same volume of normal saline.Nerve function was evaluated by the Longa method.Cerebral cognitive function(escape time and times of error response)was assessed by Y maze experiment.Hippocampal neuron apoptosis was detected by TUNEL assay.The expression of X-linked inhibitor of apoptosis protein(XIAP),Omi/HtrA2,poly(ADP-ribose)polymerase(PRAP),pro-caspase-3,pro-caspase-9,caspase-3 and caspase-9 was determined by Western blot.Pathological changes in the hippocampus were observed by HE staining.Results Compared with sham operation group,craniocerebral injury led to a marked increase in escape time,times of error response,score of nerve function,apoptosis rate of neurons and relative expression of PRAP,Omi/HtrA2,caspase-3,caspase-9,pro-caspase-3 and pro-caspase-9 and a significant decrease in XIAP expression,with scattered distribution of hippocampal neurons and massive loss and necrosis of neurons.Compared with craniocerebral injury group,DEX treatment reduced escape time,times of error response,score of nerve function,apoptosis rate of neurons and relative expression of PRAP,Omi/HtrA2,caspase-3,caspase-9,pro-caspase-3 and pro-caspase-9,up-regulated the expression of XIAP,inhibited neuron loss and necrosis,and improved cell arrangement.Moreover,the effects of high-dose DEX were better than those of low-dose DEX.Conclusion DEX can suppress hippocampal neuron apoptosis through inhibiting Omi/HtrA2 pathway and apoptosis-related protein expression in rats with craniocerebral injury.

关 键 词：颅脑损伤 右美托咪定 海马神经 细胞凋亡 线粒体 动物 实验 大鼠 

分 类 号：R651.1[医药卫生—外科学]