利用MR分子影像观察小鼠脑缺血再灌注损伤炎性反应的动态变化  

Dynamic changes of inflammatory response in mice with cerebral ischemia-reperfusion injury observed by MR molecular imaging

作　　者：庄丽华[1] 孔营楠 詹松华[1] 龚志刚[1] 杨烁慧[1] 陆方[1] 刘孟潇 ZHUANG Lihua;KONG Yingnan;ZHAN Songhua;GONG Zhigang;YANG Shuohui;LU Fang;LIU Mengxiao(Department of Radiology,Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Branch,Siemens Healthcare Ltd.,Shanghai 201318,China)

机构地区：[1]上海中医药大学附属曙光医院放射科,上海201203 [2]西门子医疗系统有限公司上海分部,上海201318

出　　处：《实用放射学杂志》2020年第4期657-661,679,共6页Journal of Practical Radiology

基　　金：国家自然科学基金面上项目(81573782).

摘　　要：目的利用Ferumoxytol增强MR观察小鼠脑缺血再灌注损伤急性期炎性反应的动态变化.方法将54只C57BL/6小鼠按照体质量随机分为假手术组、模型组(模型A组和模型B组),每组再分为24 h、48 h、72 h亚组,每组6只,模型A组和B组小鼠采用线栓阻塞右侧大脑中动脉制作小鼠脑缺血再灌注模型,假手术组和模型A组术后通过尾静脉注射Ferumoxytol,模型B组注射等体积生理盐水,并在相应时间点进行MR扫描,观察脑组织信号变化,测定血清炎性因子水平,HE染色观察脑组织坏死情况,IBA1免疫组化+普鲁士蓝染色观察小胶质细胞活化情况及吞噬Ferumoxytol情况.结果模型组术后出现不同程度的神经功能缺损,模型A组和模型B组血清炎性因子TNF-α和IL-1β差异无统计学意义,MR扫描显示模型A组小鼠再灌注24 h右侧脑组织可见明显T2 WI高信号,梗死区周围出现斑点状及条状负性强化区域,再灌注48 h梗死周围仍可见负性强化区域,维持至梗死后72 h.在再灌注后24 h小胶质细胞+普鲁士蓝染色阳性细胞比例最高,到72 h呈逐渐下降趋势.结论18 mg Fe/kg Ferumoxytol注射不影响脑缺血再灌注急性期炎性反应,采用Ferumoxytol增强MR可作为监测脑缺血再灌注损伤急性期炎性反应的一种有效手段,再灌注后24 h神经存在炎性反应的高峰.Objective To observe the dynamic changes of inflammatory response in the acute stage of cerebral ischaemia-reperfusion injury in mice by Ferumoxytol-enhanced MR.Methods 54 C57BL/6 mices were randomly divided into the sham-operated group and the model group(model A group and model B group)according to their body weight.Each group was further divided into 24 h,48 h and 72 h subgroups with 6 mice in each group.Mice in model A and B groups had occluding suture to block the right middle cerebral artery to make a cerebral ischaemia-reperfusion model.Mices in the sham-operated and model A groups were injected with Ferumoxytol via tail vein after operation,whereas the mices in the model B group were injected with an equal volume of physiological saline.MR was performed at corresponding time points to show the signal changes in the negative reinforcement region of brain tissue.The level of serum inflammatory factors was measured,the necrosis of brain tissue by HE staining was observed and the activation of microglia and phagocytosis of Ferumoxytol by IBA1 immunohistochemistry and Prussian blue staining were also observed.Results Different degrees of neurological deficits occurred in the model group after operation.There was no significant difference in serum inflammatory factors of TNF-α and IL-1β between model A group and model B group.MR in model A group showed obvious hyperintensity in the right hemisphere on T2WI at 24 h after reperfusion,with spot-like and strip-like negative reinforcement areas appearing around the infarction.Negative reinforcement areas were still visible around the infarction at 48 h after reperfusion.and maintained until 72 h after infarction.The proportion of microglia4-Prussian blue staining-positive cells were the highest at 24 h reperfusion and gradually decreased at 72 h.Conclusion Ferumoxytol injection of 18 mg Fc/kg does not affect the inflammatory response in the acute phase of cerebral ischaemia and reperfusion.Ferumoxytol-enhanced MR can be used as an effective method to monitor the i

关 键 词：脑缺血再灌注 FERUMOXYTOL 炎性反应 磁共振成像 

分 类 号：R743[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]