高脂血症对大鼠局灶性脑缺血再灌注后神经损伤及ROS/Nrf2通路的影响  

Effect of Hyperlipidemia on Nerve Injury after Focal Cerebral Ischemia/Reperfusion and ROS/Nrf2 Pathway in Rats

作　　者：王建平 张杰[2] 赵洪云 WANG Jian-ping;ZHANG Jie;ZHAO Hong-yun(Department 7 of Neurology;CT Diagnosis Room;Department 3 of Neulology,Cangzhou Central Hospital,Cangzhou 061000,China)

机构地区：[1]沧州市中心医院神经内七科,河北沧州061000 [2]沧州市中心医院CT诊断室,河北沧州061000 [3]沧州市中心医院神经内三科,河北沧州061000

出　　处：《南昌大学学报（医学版）》2021年第5期8-13,18,共7页Journal of Nanchang University：Medical Sciences

基　　金：河北省卫生健康委员会课题(20200305)。

摘　　要：目的探讨高脂血症(HL)对大鼠局灶性脑缺血再灌注(I/R)后神经损伤的影响及机制。方法按照随机对照表法将60只SD大鼠分为6组:正常组、假手术组、I/R组、HL组、HL+假手术组、HL+I/R组,每组各10只;正常组、假手术组、I/R组均采用低脂饲料饲养,HL组、HL+假手术组、HL+I/R组均采用高脂饲料喂养,各组大鼠均喂养8周;采用大脑中动脉局灶性栓塞法建立局灶性脑I/R模型;再灌注后24 h进行神经行为评分;TTC染色法观察脑梗死体积;TUNEL染色观察海马CA1区脑组织凋亡;试剂盒检测脑组织匀浆中谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平;western blot法检测海马CA1区脑组织中Nrf2的蛋白表达。结果正常组、假手术组、HL组和HL+假手术组大鼠神经功能评分均为0,且均未出现脑梗死;I/R组神经功能评分、脑梗死体积、海马CA1区脑组织凋亡指数均较正常组和假手术组显著增加(均P<0.05);与I/R组比较,HL+I/R组的神经功能评分、脑梗死体积以及海马CA1区脑组织凋亡指数均增加(均P<0.05),而且脑组织匀浆中SOD和GSH-Px水平及Nrf2蛋白表达量均降低,MDA水平升高(均P<0.05)。结论高脂血症可加重局灶性脑I/R的神经功能损伤,诱导神经元凋亡,其机制可能是通过ROS/Nrf2途径介导。Objective To investigate the effect and mechanism of hyperlipidemia on nerve injury after focal cerebral ischemia/reperfusion(I/R)in rats.Methods Sixty male SD rats were randomly divided into 6 groups,with 10 rats in each group.Rats in blank group,sham-operation group and I/R group were fed with normal low-fat diet,while rats in HL group,HL+sham group and HL+I/R group were given high-fat diet for 8 weeks.The modified middle cerebral artery occlusion(MCAO)method was used to establish the model of focal cerebral I/R.Neurobehavioral score was measured 24 hours after reperfusion.Cerebral infarction volume was observed by TTC staining.The apoptosis of brain tissue in hippocampal CA1 region TUNEL staining was detected.The levels of glutathione peroxidase(GSH-Px),malondialdehyde(MDA)and superoxide dismutase(SOD)in tissue homogenate were determined using kits.The expression of Nrf2 protein was measured by western blot.Results The Longa nerve function score was 0 and no cerebral infarction occurred in blank group,sham-operation group,HL group and HL+sham operation group.Compared with blank group and sham-operation group,the Longa score,cerebral infarction volume and apoptosis rate in hippocampal CA1 region increased in I/R group(P<0.05).Compared with I/R group,the Longa score,cerebral infarction volume,apoptosis rate in hippocampal CA1 region and formation of MDA increased and levels of SOD and GSH-Px and expression of Nrf2 protein decreased in HL+I/R group(P<0.05).Conclusion Hyperlipidemia can aggravate nerve injury and induce neuron apoptosis in focal cerebral I/R thorough regulating ROS/Nrf2 pathway.

关 键 词：高脂血症 局灶性脑缺血再灌注 神经损伤 活性氧簇/核因子E2相关因子 动物实验 大鼠 

分 类 号：R743.31[医药卫生—神经病学与精神病学]