机构地区:[1]陕西省人民医院麻醉科,陕西西安710068 [2]陕西省人民医院神经内科,陕西西安710068 [3]陕西省人民医院儿科,陕西西安710068
出 处:《现代生物医学进展》2021年第20期3845-3849,3887,共6页Progress in Modern Biomedicine
基 金:陕西省自然科学基础研究计划项目(2018JM7121)。
摘 要:目的:探讨右美托咪定对老年大鼠麻醉手术后对海马α-突触核蛋白表达和早期认知功能障碍的影响。方法:24只20-24个月龄SD大鼠机分为三组:对照组(不给予任何治疗,n=8),麻醉手术组(在异氟烷麻醉下进行剖腹手术,n=8),右美托咪定组(麻醉前30分钟,腹膜内注射25μg/kg右美托咪定,在异氟烷麻醉下进行剖腹手术,n=8)。通过Y迷宫和爬杆测试分别评估干预措施对认知功能和运动行为的影响。通过蛋白质免疫印迹检测干预措施对α-突触核蛋白,S100β蛋白,caspase 3,Bax和Bcl-2表达的影响。通过RT-qPCR检测干预措施对TNF-α和IL-1βm RNA表达的影响。通过酶联免疫吸附测定干预措施对ROS,MDA和ATP表达水平的影响。通过免疫组织化学分析干预措施对NDUFV2,MT-ND1,SDHA和SDHC的表达水平的影响。结果:与对照组相比,麻醉手术组试验次数和爬杆时间、α-突触核蛋白、S100β、caspase 3和Bax蛋白表达水平、TNF-α和IL-1βm RNA表达水平、ROS和MDA水平均显著增加,Bcl-2蛋白表达、ATP水平以及NDUFV2、MT-ND1、SDHA和SDHC的表达水平均显著降低(P<0.05);与麻醉手术组相比,右美托咪定组试验次数和爬杆时间、-突触核蛋白、S100β、caspase 3和Bax蛋白表达水平、TNF-α和IL-1βm RNA表达水平、ROS和MDA水平均显著降低,Bcl-2蛋白表达、ATP水平以及NDUFV2、MT-ND1、SDHA和SDHC的表达水平均显著增加(P<0.05)。结论:右美托咪定通过降低海马的炎症反应和神经元凋亡,以及增加α-突触核蛋白和S100β的水平,抑制线粒体功能障碍,保护老年大鼠麻醉术后早期认知功能障碍。Objective:To investigate the mechanism of dexmedetomidine on the expression ofα-synuclein in hippocampus and early cognitive dysfunction after anesthesia surgery in aged rats.Methods:Twenty-four SD rats aged 20-24 months were divided into three groups:control group(no treatment,n=8),anesthesia group(laparotomy under isoflurane anesthesia,n=8),dexmedetomidine group(before anesthesia)In 30 minutes,25μg/kg dexmedetomidine was injected intraperitoneally,and laparotomy was performed under isoflurane anesthesia,n=8).The Y maze and pole climbing tests were used to evaluate the effects of interventions on cognitive function and motor behavior.Western blot was used to detect the effect of intervention measures on the expression ofα-synuclein,S100βprotein,caspase 3,Bax and Bcl-2.The effect of intervention measures on the expression of TNF-αand IL-1βmRNA was detected by RT-qPCR.The effect of intervention measures on the expression levels of ROS,MDA and ATP was determined by enzyme-linked immunosorbent assay.The influence of intervention measures on the expression levels of NDUFV2,MT-ND1,SDHA and SDHC was analyzed by immunohistochemistry.Results:Compared with the control group,the number of trials and pole climbing time,α-synuclein,S100β,caspase 3 and Bax protein expression levels,TNF-αand IL-1βmRNA expression levels,ROS and MDA levels in the anesthesia surgery group increased significantly,while Bcl-2 protein expression,ATP level and the expression levels of NDUFV2,MT-ND1,SDHA and SDHC were significantly reduced(P<0.05);Compared with the anesthesia surgery group,the number of trials and pole climbing time,α-Synuclein,S100β,caspase 3 and Bax protein expression levels,TNF-αand IL-1βmRNA expression levels,and ROS and MDA levels in the dexmedetomidine group were significantly reduced,while the expression of Bcl-2 protein,ATP level and the expression levels of NDUFV2,MT-ND1,SDHA and SDHC increased significantly(P<0.05).Conclusion:Dexmedetomidine inhibits mitochondrial dysfunction by reducing hippocampal inflammatio
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