合成MRI评估高血糖大鼠脑缺血再灌注早期血脑屏障结构和基质金属蛋白酶9表达  

Synthetic MRI for evaluating structure of blood-brain barrier and matrix metalloproteinases-9 expression in early stage of cerebral ischemia reperfusion in hyperglycemic rats

作　　者：李鹏 马艳梅[1] 杨晶 陈兵 李艳[2] 徐洁[1] 张建忠 景丽 LI Peng;MA Yanmei;YANG Jing;CHEN Bing;LI Yan;XU Jie;ZHANG Jianzhong;JING Li(Department of Pathology,School of Basic Medical Science,Ningxia Medical University,Yinchuan 750004,China;Department of Radiology,General Hospital of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学基础医学院病理学系,宁夏银川750004 [2]宁夏医科大学总医院放射科,宁夏银川750004

出　　处：《中国医学影像技术》2023年第5期651-656,共6页Chinese Journal of Medical Imaging Technology

摘　　要：目的 观察高血糖大鼠脑缺血再灌注(CIR)早期血脑屏障(BBB)结构和基质金属蛋白酶9(MMP-9)表达及其与合成MRI(syMRI)定量参数的关系。方法 选取SD雄性大鼠30只,随机分为高血糖短暂性大脑中动脉栓塞再灌注(tMCAOR)组(HG组,n=12)、正常血糖tMCAOR组(NG组,n=12)及正常血糖假手术组(Sham组,n=6)。行syMRI-T2WI,观察每组大鼠脑梗死体积百分比,计算相对T1(rT1)值、相对T2(rT2)值和相对质子密度(rPD)值。采用免疫组织化学染色观察免疫球蛋白G(IgG)外渗和MMP-9含量。采用蛋白质印迹法检测BBB紧密连接蛋白[闭锁小带蛋白1(ZO-1)、闭合蛋白(Occludin)、紧密连结蛋白-5(Claudin-5)]和MMP-9表达水平。结果 HG组、NG组及Sham组分别有9、9及6只大鼠建模成功。HG组大鼠脑梗死体积百分比、rT1值、rT2值、rPD值、IgG染色光密度、MMP-9染色光密度及MMP-9表达水平均高于NG组(P均<0.05),而ZO-1、Occludin及Claudin-5表达水平均低于NG组(P均<0.05);Sham组均未见明显异常。CIR早期,rT1、rT2和rPD值均与IgG染色光密度(r=0.727、0.797、0.732,P均<0.01)及MMP-9染色光密度(r=0.673、0.674、0.597,P均<0.05)呈正相关。结论 高血糖大鼠CIR早期BBB结构被破坏、MMP-9表达上调;且梗死区rT1、rT2和rPD值均与IgG外渗及MMP-9表达水平有关。Objective To observe the structure of blood-brain barrier(BBB)and the expression of matrix metalloproteinases-9(MMP-9)in early stage of cerebral ischemia reperfusion(CIR)in hyperglycemic rats,and to explore the relationships with synthetic MRI(syMRI)quantitative parameters.Methods Thirty SD male rats were randomly divided into hyperglycemia transient middle cerebral artery occlusion reperfusion(tMCAOR)group(HG group,n=12),normoglycemia tMCAOR group(NG group,n=12)and normoglycemia sham operation group(Sham group,n=6).The syMRI-T2WI was acquired to observe the percentage of cerebral infarction volume,while relative T1(rT1)value,relative T2(rT2)value and relative proton density(rPD)value were calculated.Immunohistochemistry staining was performed to observe the extravasation of immunoglobulin G(IgG)and the content of MMP-9.The expression levels of BBB tight junction proteins(zonula occludens-1[ZO-1],Occludin,Claudin-5)and MMP-9 were detected with Western blotting.Results Nine,nine,and six rats in the HG group,NG group,and Sham group were successfully modeled,respectively.The percentage of cerebral infarction volume,rT1 value,rT2 value,rPD value,IgG staining optical density,MMP-9 staining optical density and MMP-9 expression level in HG group were higher than those in NG group(all P<0.05),while ZO-1,Occludin and Claudin-5 expression level in HG group were lower than those in NG group(all P<0.05).No obvious abnormality was found in Sham group.In early stage of CIR,rT1,rT2 and rPD values were positively correlated with IgG staining optical density(r=0.727,0.797,0.732,all P<0.01)and MMP-9 staining optical density(r=0.673,0.674,0.597,all P<0.05).Conclusion BBB structure was damaged and the expression of MMP-9 was up-regulated in early stage of CIR in hyperglycemic rats,and rT1,rT2 and rPD values of cerebral infarction area were related to IgG extravasation and MMP-9 expression level.

关 键 词：大鼠 高血糖 血脑屏障 脑损伤 大脑中动脉 基质金属蛋白酶9 磁共振成像 

分 类 号：R651.1[医药卫生—外科学] R445.2[医药卫生—临床医学]