靶向调节GSK-3β基因对急性一氧化碳中毒大鼠脑损伤的保护作用研究  

Protective Effect of Targeted Regulation of GSK-3β Gene on Brain injury in Rats with Acute Carbon Monoxide Poisoning

作　　者：吴启仙 宁红平 吴兴辉 李厚成 WU Qi-xian;NING Hong-ping;WU Xing-hui;LI Hou-cheng(Department of Hyperbaric Oxygen,Taihe Hospital of Shiyan City Affiliated Hospital of Hubei University of Medicine,Shiyan,Hubei 442000,China)

机构地区：[1]十堰市太和医院湖北医药学院附属医院高压氧科,湖北十堰442000

出　　处：《解放军医药杂志》2021年第10期15-20,共6页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

摘　　要：目的探讨靶向调节糖原合成激酶-3β(GSK-3β)基因对急性一氧化碳(CO)中毒大鼠脑损伤的保护作用。方法选取清洁级SD大鼠80只,随机分为正常对照组、CO中毒模型组、慢病毒空白组(LV-EGFP转染大鼠双侧海马体)、GSK-3β低表达组(LV-GSK-3β转染大鼠双侧海马体),每组20只。测定大鼠逃避潜伏期、经过原平台位置次数、原平台象限停留时间,测定并比较神经细胞凋亡水平、大鼠海马组织GSK-3β、信号转导及转录激活因子3(STAT3)蛋白和mRNA表达水平。结果与正常对照组比较,CO中毒模型组、慢病毒空白组、GSK-3β低表达组逃避潜伏期延长,脑组织神经细胞凋亡水平、海马组织GSK-3β、STAT3 mRNA和蛋白表达明显升高,经过原平台位置次数减少、原平台象限停留时间缩短(P<0.05)。与CO中毒模型组、慢病毒空白组比较,GSK-3β低表达组逃避潜伏期缩短,脑组织神经细胞凋亡水平、海马组织GSK-3β、STAT3 mRNA和蛋白表达明显降低,经过原平台位置次数增多、原平台象限停留时间延长(P<0.05)。结论靶向抑制GSK-3β基因表达对急性CO中毒大鼠脑损伤神经功能具有保护作用,其机制可能与靶向抑制GSK-3β可下调STAT3的表达进而减轻神经炎症反应有关。Objective To investigate the protective effect of targeted regulation of glycogen synthase kinase-3β(GSK-3β)gene on brain injury in rats with acute carbon monoxide(CO)poisoning.Methods Eighty clean SD rats were randomly divided into normal control group(n=10),CO poisoning model group(n=10),lentivirus blank group(n=10,LV-EGFP transfected bilateral hippocampus)and GSK-3βlow expression group(n=10,LV-GSK-3βtransfected bilateral hippocampus).The escape latency,the times of passing through the original platform and the quadrant retention time of the original platform were determined.Levels of neuronal apoptosis and the protein and mRNA expressions of GSK-3β,signal transducer and activator of transcription-3(STAT3)in hippocampal tissues of rats were measured and compared.Results Compared with those in normal control group,times of escape latency were prolonged,and apoptosis levels of neuronal cells in brain tissues,and mRNA and protein expressions of GSK-3βand STAT3 were significantly increased,while times of passing the original platform position and staying time of the original platform quadrant were significantly shortened in CO poisoning model group,lentivirus blank group and GSK-3βlow expression group(P<0.05).Compared with those in CO poisoning model group and lentivirus blank group,the escape latency was shortened,and apoptosis level of neuronal cells in brain tissues,mRNA and protein expressions of GSK-3βand STAT3 were significantly decreased,while times of passing through the original platform were increased,and the time of staying in the original platform quadrant was significantly prolonged in GSK-3βlow expression group(P<0.05).Conclusion Targeted inhibition of GSK-3βgene expression has a certain protective effect on neurological function,and its mechanism may be related to the downregulated STAT3 expression by targeting inhibition of GSK-3βso as to ameliorate neuroinflammatory reaction in rats with acute CO poisoning.

关 键 词：一氧化碳中毒 脑损伤 糖原合成激酶-3β 海马 细胞凋亡 大鼠 SPRAGUE-DAWLEY 

分 类 号：R-332[医药卫生] R595.1