SOD3表达在非诺贝特治疗小鼠脑缺血再灌注损伤中的作用机制  

The mechanism of SOD3 expression in the treatment of cerebral ischemia reperfusion injury in mice with fenofibrate

作　　者：马江磊 张晨芳 杨锡彤 程建杰 王光明 Ma Jiangei;Zhang Chenfang;Yang Xitong;Cheng Jianjie;Wang Guangming(Department of School of Clinical Medicine,Dali University,Yunnan 671000,China)

机构地区：[1]大理大学临床医学院,云南671000 [2]大理大学第一附属医院基因检测中心 [3]烟台毓璜顶医院神经内科

出　　处：《脑与神经疾病杂志》2024年第7期419-423,共5页Journal of Brain and Nervous Diseases

基　　金：国家自然科学基金项目(82160244);云南省地方高校联合专项项目(202001BA070001-156);云南省卫计委医学学科带头人项目(D-2017057);云南省教育厅科学研究基金项目(2023Y0989);大理大学第一附属医院重点建设项目(大附院发(2021)34号)。

摘　　要：目的探究SOD3的表达在非诺贝特治疗缺血再灌注(I/R)机制中的作用。方法使用基因敲除技术构建SOD3基因敲除的小鼠,通过PCR技术和DNA测序技术鉴定SOD3小鼠的基因分型,蛋白印迹法检测SOD3蛋白的表达。将野生型和SOD3^(-/-)型小鼠随机分为4组,野生型对照羟甲基纤维素(CMC)组(6只)、野生型非诺贝特治疗(Feno)组(6只)、SOD3^(-/-)型CMC对照(SOD3.CMC)组(5只)、SOD3^(-/-)型非诺贝特治疗(SOD3.Feno)组(5只)。使用线栓法制作小鼠大脑中动脉栓塞模型,栓塞90 min后拔出栓线,脑I/R 60 min处死小鼠。手术过程中用脑血流监测仪测局部脑血流,TTC染色后,分析各组脑梗死情况。结果PCR和DNA测序分析显示成功构建SOD3^(-/-)小鼠。I/R后,各组脑血流比较差异无统计学意义(P>0.05)。Feno组较CMC组的脑梗死体积明显缩小(P<0.001);SOD3.Feno组较SOD3.CMC组梗死体积缩小(P<0.001);SOD3.Feno组梗死面积较Feno组显著增加(P<0.05)。结论SOD3的表达是非诺贝特治疗脑I/R损伤的机制之一。Objective To explore the role of SOD3 expression in the mechanism of fenofibrate in the treatment of ischemia reperfusion(I/R).Methods The SOD3 gene knockout mice were constructed by gene knockout technology,and their genotypes were identified by PCR technology and DNA sequencing technology.The expression of SOD3 protein was detected by Western blot.Wild type and SOD3^(-/-)type mice were randomly divided into four groups:wild type CMC control(CMC)group(6 mice),wild type fenofibrate treatment(Feno)group(6 mice),SOD3^(-/-)type CMC control(SOD3.CMC)group(5 mice),SOD3-/type fenofibrate treatment(SOD3.Feno)group(5 mice).A mouse model of middle cerebral artery occlusion was created using the thread occlusion method.After 90 minutes of occlusion,the thread was removed and the cerebral blood flow was I/R for 60 minutes to execute the mouse.During the surgery,the local cerebral blood flow was measured using a cerebral blood flow monitor,and after TTC staining,the situation of cerebral infarction in each group was analyzed.Results PCR and DNA sequencing analysis showed that SOD3^(-/-)mice were successfully constructed.After I/R,there was no significant difference in cerebral blood flow among the groups(P>0.05).The volume of cerebral infarction in the Feno group was significantly reduced compared to the CMC group(P<0.001);The infarct volume in the SOD3.Feno group decreased compared to the SOD3.CMC group(P<0.001);The infarct area in the SOD 3.Feno group was significantly increased compared to the feno group(P<0.05).Conclusion The expression of SOD3 is one of the mechanisms of fenofibrate in the treatment of cerebral ischemia-reperfusion injury.

关 键 词：脑缺血再灌注损伤 非诺贝特 SOD3 小鼠 

分 类 号：R743[医药卫生—神经病学与精神病学]