基于多参数MRI探讨大鼠脑缺血再灌注对脑细胞毒性水肿的影响  

Exploring the effect of cerebral ischemia-reperfusion on cerebral cytotoxic edema in rats based on multiparameter MRI

作　　者：胡少坤 肖培伦 张海默 李天睿 陈超 于淼 王晓莉 HU Shaokun;XIAO Peilun;ZHANG Haimo;LI Tianrui;CHEN Chao;YU Miao;WANG Xiaoli(School of Medical Imaging,Shandong Second Medical University,Weifang 261053,China;Department of Human Anatomy,School of Basic Medical Sciences,Shandong Second Medical University,Weifang 261053,China)

机构地区：[1]山东第二医科大学医学影像学院,潍坊261053 [2]山东第二医科大学基础医学院人体解剖学教研室,潍坊261053

出　　处：《神经解剖学杂志》2024年第5期541-548,共8页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(82071888);山东省中医药科技发展计划(Q-2023071);山东省大学生创新训练计划(S202310438211);校级大学生创新训练计划(X2023212,X2023641)。

摘　　要：目的:采用T2加权成像(T2WI)、弥散加权成像(DWI)、脉冲梯度自旋回波(PGSE)等多参数MRI扫描结合多种组织病理学技术观察大鼠脑缺血不同时间后再灌注(CIRI)对脑组织细胞毒性水肿的影响,为缺血性脑卒中模型的建立及临床诊疗提供依据。方法:健康成年雄性Sprague Dawley大鼠按照随机数字表法分为假手术(Sham)组、缺血60 min再灌注(IR-60 min)组、IR-120 min组及IR-180 min组。改良Zea Longa线栓法建立大鼠CIRI模型,激光多普勒血流仪结合苏木精-伊红(HE)染色法鉴定模型;多参数MRI扫描、结合脑含水量、水通道蛋白4(AQP4)免疫荧光染色、Western Blot等方法,观察各组大鼠脑组织细胞毒性水肿及肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)的变化。结果:HE染色及脑组织含水量结果示,随缺血时间的延长,缺血侧大脑皮质水肿程度加重;T2WI结果示,IR-60 min组损伤开始累及大脑皮质,IR-120 min组损伤已完全累及大脑皮质,IR-180 min组损伤最重(P<0.05),大脑中线明显向对侧移位。各缺血侧大脑皮质相对表观弥散系数、水交换时间均显著低于Sham组(P<0.05),且呈上升趋势;各缺血侧大脑皮层细胞膜通透性均显著高于Sham组(P<0.05)。缺血侧大脑皮质AQP4、IL-1β、TNF-α表达显著高于Sham组,且呈上升趋势(P<0.05)。结论:大鼠大脑中动脉缺血60、120及180 min后再灌注均可导致脑损伤,且缺血时间的延长会加重脑细胞毒性水肿,120 min是CIRI模型的最佳缺血时间;多参数MRI可活体监测大鼠CIRI后脑组织微结构变化,为早期临床诊疗提供可视化依据。Objective:Using T2-weighted imaging(T2WI),diffusion-weighted imaging(DWI),pulsed gradient spin echo(PGSE)multiparametric magnetic resonance imaging combined with various histopathological techniques to observe the effects of reperfusion after different times of cerebral ischemia(CIRI)on the cytotoxic edema of brain tissues in rats.This provides a solid foundation for the establishment of ischemic stroke models and clinical diagnosis and treatment.Methods:Healthy adult male Sprague Dawley rats were randomly allocated to four groups:the sham-operated(Sham)group,the ischaemia 60 min reperfusion(IR-60 min)group,the IR-120 min group,and the IR-180 min group.CIRI rat model was prepared by modified Zea Longa method.Laser doppler flowmetry combined with hematoxylin-eosin(HE)staining was employed to identify the model.Multiparametric magnetic resonance imaging,combined with water content of brain,immunofluorescence staining of aquaporin-4(AQP4),and Western Blot were performed to observe cytotoxic edema of brain tissues and tumour necrosis factor alpha(TNF-α),interleukin 1β(IL-1β)in brain tissue of rats in each group.Results:HE staining and determination of brain tissue water content prove that as ischemia time prolongs,the degree of cerebral cortex edema on the ischemic side increases.The T2WI results showed that the injury in the IR-60 min group began to affect the cerebral cortex,the injury in the IR-120 min group had completely affected the cerebral cortex,and the injury in the IR-180 min group was the most severe(P<0.05),with a significant shift of the midline of the brain towards the opposite side.The relative apparent diffusion coefficient and water exchange time of the cerebral cortex on the ischemic side of the rats were found to be significantly lower than those of the sham group,with an declining trend(P<0.05).Additionally,the values of cell membrane permeability of the cerebral cortex on the ischemic side of the rats were observed to be significantly higher than those of the sham group in all groups(P<0.05).

关 键 词：多参数磁共振成像(mMRI) 脑缺血再灌注损伤(CIRI) 水通道蛋白4(AQP4) 脑水肿 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学] R445.2[医药卫生—临床医学]