人体白蛋白早期干预降低延迟溶栓后血脑屏障通透性的实验研究  

Early intervention with human albumin to reduce the tissue plasminogen activator-mediated blood-brain barrier permeability damaged by delayed reperfusion:an experimental study in rats

作　　者：鲁海涛[1] 赵俊功[1] 李明华[1] 李永东[1] 张培蕾[1] 

机构地区：[1]上海交通大学附属第六人民医院介入和放射诊断研究所,200233

出　　处：《介入放射学杂志》2011年第10期803-809,共7页Journal of Interventional Radiology

基　　金：上海市自然科学基金(09ZR1424400)

摘　　要：目的探讨人体白蛋白早期干预对延迟溶栓所致的血脑屏障通透性的影响,为降低延迟溶栓后血管源性脑水肿的防治提供依据。方法采用颈内动脉线栓法建立脑缺血模型,然后分别在脑缺血2、3、4 h后拔出线栓形成脑缺血再灌注模型。138只体重320～380 g的清洁级雄性SD大鼠被随机分为假手术组、对照组、白蛋白组和联合治疗组(白蛋白+rt-PA),其中假手术组3只,其余每组再分为脑缺血2、3、4 h再灌注亚组,每亚组15只。在白蛋白组、联合治疗组中,20%人体白蛋白于大脑中动脉阻塞(MCAO)2 h时间点经大鼠股静脉给药,剂量2.5 g/kg体重。联合治疗组于各再灌注时间点拔栓后立即自大鼠股静脉注入rt-PA,剂量10 mg/kg。各组大鼠于MCAO后24 h处死,分别行2,3,5-氯化三苯基四氮唑(TTC)染色测量梗死体积、埃文斯蓝(EB)定量检测血脑屏障(BBB)渗漏情况以及免疫组化法检测基质金属蛋白酶9(MMP-9)的表达。结果大剂量人体白蛋白早期干预显著改善了24 h后大鼠的神经功能评分,MCAO 3 h、MCAO 4 h白蛋白组及MCAO 3 h联合治疗组大鼠神经功能明显好于对照组(P<0.05);MCAO 4 h联合治疗组较对照组神经功能评分有所改善,但差异无统计学意义(P>0.05)。白蛋白组、联合治疗组各缺血再灌注时间点与对照组相应时间点比较梗死体积有明显缩小,组间差异有统计学意义(P<0.05),尤其是在MCAO 4 h白蛋白组、联合治疗组分别较对照组下降23%和17.3%。脑出血转化在对照组4 h出现2例、白蛋白组4 h、联合治疗组4 h各1例。白蛋白组、联合治疗组各缺血再灌注时间点与对照组相应时间点比较EB含量有明显降低(P<0.05)。与对照组相比,白蛋白组、联合治疗组的MMP-9在梗死灶边缘表达阳性细胞数显著减少。结论大剂量人体白蛋白早期干预,可降低实验动物延迟溶栓后的BBB的通透性,减小梗死体积。Objective To clarify whether early use of high-dose human albumin can reduce the permeability of blood-brain barrier（BBB） damaged by delayed thrombolysis or not,and,in turn,reduce the vasogenic brain edema.Methods A total of 138 male SD rats weighing 320-380 grams were randomly divided into 4 groups： sham operation group（n = 3）,control group（n = 45）,albumin group（n = 45） and albumin＋rt-PA group（n = 45）.According to the reperfusion time after the onset of middle cerebral artery occlusion（MCAO）,each group,except sham operation group,was divided into three subgroups of 2 h,3 h and 4 h with 15 rats in each subgroup.Rats in albumin group and albumin＋rt-PA group received an intravenous infusion of 20% human albumin（2.5 g/kg） 2 hours after the onset of MCAO,and rats in albumin＋rt-PA group received an intravenous infusion of rt-PA（10 mg/kg） at all points of reperfusion time via the rat＇s femoral vein immediately after the reperfusion.All rats were sacrificed 24 hours after MCAO,the infarct volume of the brain was determined with TTC dye method,the leakage extent of BBB was quantitatively estimated by using Evans blue method,and the matrix metalloproteinase-9（MMP-9） expression was assessed with immunohistochemistry technique.Results Early intervention with the use of high-dose human albumin could significantly improve the neurological score at 24 h.In MCAO 3 h albumin group,MCAO 4 h albumin group and MCAO 3 h albumin＋rt-PA group,neurological score was significantly better than that in the control group（P 0.05）.The neurological score was improved more remarkably in albumin＋rt-PA group of MCAO 4 h than in the control group,although the difference was of no statistical significance（P 0.05）.The volume of the infarct tissue was also significantly smaller in all the treated groups with high-dose human albumin groups（P 0.05） when compared with the control group.The infarct volume of the MCAO 4 h in albumin group and albumin＋rt-PA group was reduced by 23% and by 17.3

关 键 词：急性脑缺血 大脑中动脉阻塞 溶栓 人体白蛋白 血脑屏障 时间窗 

分 类 号：R743.3[医药卫生—神经病学与精神病学]