小鼠急性脑缺血再灌注损伤后消化道不同肠段通透性的改变  

Changes of permeability in different intestinal segments of mice after cerebral ischemia-reperfusion injury

作　　者：张芯 郭卿 王斌苏 杨国红 蔡伟 牛秀珑 姬文婕 杨宁 周欣 李玉明 ZHANG Xin;GUO Qin;WANG Bin-su;YANG Guo-hong;CAI Wei;NIU Xiu-long;JI Wen-jie;YANG Ning;ZHOU Xin;LI Yu-ming(Heart Center,Characteristic Medical Center of Chinese People's Armed Police Force,Tianjin 300162,China;Department of Respiratory and Critical Care Medicine,Characteristic Medical Center of Chinese People's Armed Police Force,Tianjin 300162,China;Heart Center,3Department of Respiratory and Critical Care Medicine,Characteristic Medical Center of Chinese People’s Armed Police Force,Tianjin 300162,China)

机构地区：[1]武警特色医学中心心脏中心,天津300162 [2]天津市心血管重塑与靶器官损伤重点实验室,天津300162 [3]武警特色医学中心呼吸与重症医学科,天津300162

出　　处：《解放军医学杂志》2019年第4期271-275,共5页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(81600328);天津市科技计划项目(15ZXJZSY00010;16ZXMJSY00130)~~

摘　　要：目的研究小鼠急性脑缺血再灌注(MCAO)损伤后消化道不同肠段的通透性改变情况。方法 72只小鼠随机分为正常对照组(n=18)、假手术组(n=18)和脑缺血再灌注组(MCAO组,n=36)。采用线栓法制备小鼠MCAO损伤模型,脑组织TTC染色验证模型是否成功并计算梗死面积,采用异硫氰酸荧光标记的右旋糖酐(FD4)法检测术后1、2、3d肠道通透性变化,并于术后2d检测小鼠远端小肠、盲肠和结肠的肠道通透性,HE染色法及透射电子显微镜(TEM)观察小鼠结肠组织病理学及超微结构的变化。结果 TTC染色可观察到明显的脑梗死部位,表明MCAO模型制备成功。FD4法检测肠道通透性显示MCAO组小鼠术后1、2、3d的血浆FD4浓度均高于正常对照组和假手术组,差异有统计学意义(P<0.05);MCAO组小鼠血浆FD4浓度与脑梗死面积百分比呈明显正相关(r=0.734,P<0.001);MCAO组小鼠远端小肠、盲肠和结肠的血浆FD4浓度均高于正常对照组和假手术组[分别为(18.53±3.92)mg/L vs.(5.01±2.25)mg/L、(6.27±2.37)mg/L,(3.00±0.87)mg/L vs.(0.71±0.18)mg/L、(0.76±0.22)mg/L,(10.38±4.73)mg/L vs.(1.66±0.47)mg/L、(2.54±0.67)mg/L],差异有统计学意义(P<0.001),而正常对照组与假手术组比较差异无统计学意义(P>0.05);结肠段MCAO组血浆FD4浓度约为同肠段假手术组的4.1倍,高于其他两个肠段的增高幅度(盲肠3.9倍;小肠远端3.0倍)。病理学观察可见MCAO小鼠结肠上皮损伤及绒毛不规则,并有炎性细胞浸润,透射电镜检测发现结肠黏膜上皮紧密连接疏松且间隙增宽。结论小鼠MCAO损伤后各肠段通透性均不同程度增加,尤以结肠改变最为显著。Objective To explore the changes of permeability in different intestinal segments of mice after cerebral ischemia-reperfusion injury(middle cerebral artery occlusion,MCAO).Methods Seventy-two mice were randomly divided into control group(n=18),sham group(n=18)and MCAO group(n=36).The mice model of cerebral ischemia-reperfusion injury was established by suture-occluded method,TTC staining of brain tissue was performed to confirm the success of the model and calculate the infarct area.Fluorescein isothiocyanate-dextran(FD4)method was employed to detect the changes of intestinal permeability 1d,2d and 3d after operation,then the permeability of distal small intestine,cecum and colon was detected 2d after the intestinal permeability had been most pronounced.The pathological changes of intestinal mucosa in colon were observed with HE staining and the ultrastructural changes were observed by use of transmission electron microscope(TEM).Results TTC staining showed the obvious cerebral infarction area,and the MCAO models were successfully established.Detection of intestinal permeability by FD4 method showed that the plasma FD4 concentration was higher in MCAO group than in control and sham group 1d,2d and 3d after operation with statistical significance(P<0.05),and correlation analysis indicated a significant positive correlation between FD4 concentration and the percentage of cerebral infarction area(r=0.734,P<0.001).The plasma FD4 concentrations of distal small intestine,cecum and were higher in MCAO group[(18.53±3.92)mg/L,(3.00±0.87)mg/L,(10.38±4.73)mg/L]than in control group[(5.01±2.25)mg/L,(0.71±0.18)mg/L,(1.66±0.47)mg/L]and sham group[(6.27±2.37)mg/L,(0.76±0.22)mg/L,(2.54±0.67)mg/L]with statistical significance,while no statistical significance between control and sham group(P>0.05);the permeability of colon increased about 4.1-fold in MCAO group than in sham group[(10.38±4.73)mg/L vs.(2.54±0.67)mg/L,P<0.001].Pathological observation found the colonic mucosa was injured with villi shape irregularity and

关 键 词：脑缺血再灌注损伤 肠 通透性 小鼠 

分 类 号：R54[医药卫生—心血管疾病]