静脉注射feraheme对永久性大脑中动脉闭塞小鼠脑梗死体积和炎症反应的影响  

Effect of intravenous feraheme on cerebral infarction volume and inflammatory response in mice with permanent middle cerebral artery occlusion

作　　者：庄丽华[1] 詹松华[1] 龚志刚[1] 杨烁慧[1] 陆方[1] 孔营楠 刘孟潇 Zhuang Lihua;Zhan Songhua;Gong Zhigang;Yang Shuohui;Lu Fang;Kong Yingnan;Liu Mengxiao(Department of Radiology,Shuguang Hospital,Shagnhai Unvers ity of T raditioncd Chinese Medicine,Shagnhcd 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,201203 [2]西门子医疗系统有限公司上海分部,201318

出　　处：《国际脑血管病杂志》2019年第1期31-36,共6页International Journal of Cerebrovascular Diseases

基　　金：国家自然科学基金(81573782,81403204).

摘　　要：目的探讨静脉注射超微超顺磁氧化铁纳米颗粒feraheme(通用名ferumoxytol)对永久性大脑中动脉闭塞小鼠脑梗死体积和炎症反应的影响。方法30只C57BL/6J小鼠,采用随机数字表法随机分为假手术组、生理盐水对照组和feraheme组,每组10只。生理盐水对照组和feraheme组采用改良线栓法制作永久性右侧大脑中动脉闭塞模型,假手术组不插入栓线。模型制作后24 h进行尾静脉注射干预,其中假手术组和feraheme组注射18 mg/kg feraheme,生理盐水对照组注射等体积生理盐水。在模型制作后24 h(注射feraheme或生理盐水前)和48 h(MRI检查前)时进行神经行为学评分。模型制作后48 h行MRI扫描,根据T2加权成像计算脑梗死体积。扫描结束后采集眼眶血,用于血清肿瘤坏死因子(tumor necrosis factor,TNF)-α、白细胞介素(interleukin,IL)-1β、IL-6水平检测。然后处死小鼠取脑组织进行HE染色、Iba1免疫组化染色。结果生理盐水对照组与feraheme组脑梗死体积和神经功能评分差异均无统计学意义。生理盐水对照组和feraheme组血清TNF-α、IL-1β和IL-6均显著高于假手术组(P均<0.05),但生理盐水对照组与feraheme组之间差异无统计学意义。结论小鼠脑缺血后24 h静脉注射18 mg/kg feraheme不会影响梗死体积及炎症反应,提示该剂量feraheme可用于脑缺血后炎症反应的分子影像学研究。Objective To investigate the effect of intravenous ultrafine superparamagnetic iron oxide nanoparticles feraheme(generic name:ferumoxytol)on cerebral infarction volume and inflammatory response in mice with permanent middle cerebral artery occlusion.Methods Thirty C57BL/6J mice were divided into sham operation group,saline control group,and feraheme group by the random number table(n=10 in each group).A permanent right middle cerebral artery occlusion model was induced by the modified suture method in the saline control group and the feraheme group,and no suture was inserted into the mice of the sham operation group.The intervention was performed by tail vein injection at 24 h after modeling.The sham operation group and the feraheme group were injected with 18 mg/kg feraheme,and the saline control group was injected with the same volume of normal saline.The neurobehavioral scores were conducted at 24 h(before the feraheme or saline injection)and 48 h(before the MRI exam)after modeling.MRI scans were performed at 48 h after modeling,and the cerebral infarction volume was calculated according to T2-weighted imaging.After the end of the scan,orbital blood was collected for the detection of serum tumor necrosis factor(TNF)-α,interleukin(IL)-1β,and IL-6 levels.Then,the mice were sacrificed and the brain tissue was taken for HE staining and Iba1 immunohistochemical staining.Results There were no significant differences in the infarct volume and neurological function score between the saline control group and the feraheme group.The serum levels of TNF-α,IL-1β,and IL-6 in the saline control group and the feraheme group were significantly higher than those in the sham operation group(P<0.05),but there was no significant difference between the saline control group and the feraheme group.Conclusion Intravenous injection of 18 mg/kg feraheme at 24 h after cerebral ischemia did not affect the infarct volume and inflammatory response,suggesting that this dose of feraheme can be used for molecular imaging studies of inflamm

关 键 词：脑缺血 脑梗死 四氧化三铁 炎症 小胶质细胞 磁共振成像 疾病模型 动物 小鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]