紧密连接蛋白1与肝性脑病大鼠模型血脑屏障通透性的关系  

Relationship between zonula occludens-1 and blood-brain barrier permeability in rats with hepatic encephalopathy

作　　者：胡立华[1] 陈鹏[1] 王晓丽[1] 张继晔[1] 苏连明[1] 张沛怡[1] 

机构地区：[1]黑龙江省医院消化内科,哈尔滨150036

出　　处：《临床肝胆病杂志》2015年第4期582-584,共3页Journal of Clinical Hepatology

摘　　要：目的研究肝性脑病(HE)大鼠脑组织紧密连接蛋白(ZO)1水平与血脑屏障通透性改变之间的关系。方法将180只健康雄性SD大鼠随机分为对照组、实验组HE 4、8和12 h共4组,每组45只。应用D-氨基半乳糖(400 mg/kg)和内毒素(100μg/kg)联合腹腔内注射建立HE大鼠模型。分别于造模后4、8和12 h检测血氨浓度、伊文思蓝(EB)含量、脑组织含水量及real-time Q-PCR法检测血脑屏障ZO-1 mRNA含量。计量资料方差齐时采用LSD检测,方差不齐时采用Dunnett T3法检测。结果造模2 h后HE组大鼠逐渐出现HE症状;造模后4 h与正常组相比,大鼠血氨浓度[(74.27±1.77)μmol/L vs(33.85±1.50)μmol/L]、脑组织EB含量[(4.84±0.43)μg/g vs(3.96±0.48)μg/g]、脑组织含水量[(78.63±0.46)%vs(76.07±0.39)%]即开始升高(P值均<0.001),且随时间延长,血氨浓度、脑组织EB含量、含水量升高更加明显(F值分别为5983.36、111.54、737.25,P值均<0.001);造模后4 h大鼠脑组织ZO-1 mRNA表达的相对含量[(1.282 3±0.057 4)vs(1.457 6±0.065 4)]即开始下降(P<0.001),且随时间延长,脑组织ZO-1 mRNA表达的相对含量下降更加明显(F=135.38,P<0.001)。结论 HE时出现血脑屏障通透性增强及脑水肿,可能与ZO-1 mRNA表达下降有关。Objective To investigate the relationship between zonula occludens-1 （ZO-1 ）level and blood-brain barrier permeability in rats with hepatic encephalopathy （HE）.Methods One hundred and eighty Sprague-Dawley rats were equally and randomly divided into control and HE （4,8,and 12 h）groups of 45 animals each.Rats were given D -galactosamine （400 mg/kg）and lipopolysaccharide （100 μg/kg）by intraperitoneal injection to build an HE model.At 4,8,and 12 h after injection,blood ammonia concentration,Evans blue （EB）content,and brain water content were measured,and ZO-1 mRNA level in the blood-brain barrier was assayed by real-time Q-PCR.Measurement data were analyzed using the least significant difference test （with homogeneous variances）and Dunnett T3 test （with heterogeneous variances）.Results At 2 h after injection,the rats in the HE groups began to show HE symptoms.At 4 h after injection, the rats showed significant increases （P〈0.001 for all）relative to the controls in blood ammonia concentration （74.27 ±1.77 μmol/L vs 33.85 ±1.50 μmol/L,）,EB content （4.84 ±0.43 μg/g vs 3.96 ±0.48 μg/g）,and brain water content （78.63 ±0.46% vs 76.07 ± 0.39%）;the increases in the above three indices became more significant over time in the three HE groups （F=5983.36,111.54,and 737.25,respectively;P〈0.001 for all）.In contrast,ZO-1 mRNA expression in rat brain tissue began to decrease at 4 h after injection compared with the control （1.282 3 ±0.057 4 vs 1.457 6 ±0.065 4,P〈0.001）;the decrease in the relative ZO-1 mRNA expression level became more significant over time （F=135.38,P〈0.001 ）.Conclusion Blood-brain barrier permeability enhancement and brain edema in HE rats may be associated with the decrease in ZO-1 mRNA expression.

关 键 词：肝性脑病 紧密连接部 血脑屏障 通透性 大鼠 SPRAGUE-DAWLEY 

分 类 号：R966[医药卫生—药理学]