摘要
目的通过对大鼠大脑中动脉栓塞(MCAO)模型脑缺血区组织的扩散张量成像(DTI)评价,探讨小干扰核糖核酸(siRNA)下调水通道蛋白-4(AQP-4)对脑梗死大鼠的脑保护作用。方法将120只SD大鼠随机分为三组,每一组分为四个亚组包括慢病毒干预组、生理盐水组、MCAO组、假手术组,每组各10只。模型制备成功后,分别在1 h、3 h、6 h、12 h、24 h行改良神经功能缺陷评分(mNSS)和磁共振图像采集;每组在各个时间点取2只大鼠分别进行免疫组织化学染色及Western blot以测定缺血侧脑组织AQP-4蛋白表达。使用SPSS 22.0软件进行统计学处理,P<0.05为差异有统计学意义。结果缺血后1 h、3 h、6 h、12 h、24 h,慢病毒干预组的mNSS评分较MCAO组低,差异具有统计学意义(P<0.05)。MCAO组及生理盐水组的梗死区表观扩散系数(ADC)值、各向异性分数(FA)值均低于假手术组,12 h降至最低,随后略有升高;缺血后各时间点慢病毒干预组的ADC值、FA值均较MCAO组升高,且差异有统计学意义。ADC值、FA值在各个时间点的差异均具有统计学意义(P<0.05)。MCAO组、生理盐水组缺血后与假手术组相比,不同时间点病灶区AQP-4蛋白阳性表达均较高;慢病毒干预组各个时间点的AQP-4蛋白表达较MCAO组有所减低,且在1 h、3 h、6 h、12 h、24 h差异均具有统计学意义(P<0.05)。结论梗死区大鼠脑实质AQP-4的生成参与梗死核心区脑水肿及神经系统功能受损的发生发展,慢病毒介导的siRNA可阻止AQP-4基因表达,减轻梗死区水肿,发挥梗死后的脑保护作用,DTI可直观检测缺血性脑梗死后病灶区的改变及慢病毒注射后基因的抑制作用。
Objective To evaluate the down-regulation of aquaporin-4(AQP-4)by diffusion tensor imaging(DTI)in the ischemic region of middle cerebral artery occlusion(MCAO)model in rats with cerebral infarction.Methods Forty SD rats were randomly divided into 3 groups,then each group divided into 4 subgroups,including lentivirus intervention group,saline group,MCAO group,and sham operation group,and each group had 10 subjects.After models were successfully prepared,mNSS scores and magnetic resonance images were collected at 1 h,3 h,6 h,12 h,and 24 h respectively.Two rats from each group were taken at each time point for immunohistochemical staining and Western blot to determine the expression of AQP-4 protein in the ischemic brain tissue.SPSS 22.0 software was used for statistical analysis.The difference was statistically significant if P<0.05.Results At 1 h,3 h,6 h,12 h,and 24 h after ischemia,the mNSS scores of the lentivirus intervention group were lower than those of the MCAO group(P<0.05).The ADC values and FA values in the infarcted area of MCAO group and saline group were lower than those in the sham group,and they were lowest at 12 h and then slightly increased.The ADC values and FA values of the lentivirus intervention group was higher than that of MCAO group at different time points after ischemia,and the difference was statistically significant(P<0.05).In the MCAO group and saline group,the positive expression of AQP-4 protein in the lesion area was higher than that in the sham operation group at different time points;the expression of AQP-4 protein was lower in the lentivirus intervention group than in the MCAO group at different time points.And there were significant differences at 1 h,3 h,6 h,12 h,and 24 h(P<0.05).Conclusion The formation of brain parenchyma AQP-4 in the infarcted region is involved in the development of brain edema and impaired nervous system function in the core of infarction.Lentiviral-mediated siRNA can prevent AQP-4 gene expression,reduce infarcted edema,and play a role in infarction.The br
作者
文萌萌
张勇
程敬亮
吕青青
WEN Mengmeng;ZHANG Yong;CHENG Jingliang(Department of MRI,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan Province 450052,P.R.China)
出处
《临床放射学杂志》
CSCD
北大核心
2020年第3期609-615,共7页
Journal of Clinical Radiology
基金
国家自然科学基金项目(编号:U1404823)
国家重点研发计划项目(编号:2016YFC0103000)
