Netrin-1对大鼠实验性脑梗死后同侧丘脑血脑屏障保护作用

目的观察脑梗死后同侧丘脑是否出现血脑屏障破坏,Netrin-1对血脑屏障破坏是否具有保护作用及其能否促进神经功能恢复。方法 Sprague-Dawley大鼠36只,建立右侧大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型,假手术(sham)组仅暴露右侧大脑中动脉,分为sham组、MCAO+PBS组及MCAO+netrin-1组,每组6只。通过改良大鼠神经功能缺损评分(modified neurological severity scores,m NSS)评价神经功能,造模后第8天及第14天取材,HE染色观察梗死灶,免疫荧光检测occludin及albumin表达与分布,Western blot检测occludin及ZO-1表达水平。结果m NSS评分见予以Netrin-1后于梗死后第8天及第14天评分降低(P0.05)。HE染色见右侧皮层梗死灶。Western blot见梗死后第8天开始出现occludin减少(P0.05),第14天occludin及ZO-1均明显减少(P0.05),免疫荧光见梗死后第8天及第14天occludin减少伴albumin血管外渗出;予以Netrin-1后,western blot及免疫荧光见梗死后第14天occludin增多(P0.05),伴albumin渗出增多,ZO-1无明显变化。结论Netrin-1对大鼠实验性脑梗死后同侧丘脑血脑屏障破坏具有保护作用,并可促进梗死后神经功能恢复。

Netrin-1 Protects Blood-Brain Barrier Function in the Ipsilateral Thalamus following Focal Cerebral Infarction in Hypertensive Rats

Objective To observe the disruption of blood-brain barrier in the ipsilateral thalamus following focal cerebral infarction.And to figure out whether netrin-1 can prevent the disruption of blood-brain barrier and promote the nerve function deficient recovery.Methods 36 Sprague-Dawley rats were subjected to right middle cerebral artery occlusion (MCAO) or sham operation.There are three groups:sham group,MCAO+PBS group and MCAO+ netrin-1 group,and there are 6 rats in each group.The nerve function deficient recovery was assessed by modified Neurological Severity Score (mNSS).Rats were decapitated and their brains were removed at 8th and 14th days post MCAO or sham operation.The territory of infarction was detected by HE staining.The expression and distribution of occludin and albumin were detected by immunofluorescence.And the level of occludin and ZO-1 were detected by western blot.Results The mNSS showed the decrease in the 8th and 14th day after MCAO (P＜0.05).The HE staining showed the territory of infarction in the right cerebral cortex.Western blot showed the decrease of occludin in the 8th day after MCAO,and occludin and ZO-1 decreased significantly in the 14th day after MCAO.Immunofluorescence showed the the decrease of occludin in the 14th day after MCAO,with extravasation of albumin.After the administration of netrin-1,both western blot and immunofluorescence showed the increase of occludin in the 14th day (P＜0.05),with less extravasation of albumin.ZO-1 showed not significant difference.Conclusions Netrin-1 prevents the disruption of blood-brain barrier in the ipsilater thalamus and promote the nerve function deficient recovery following focal cerebral infarction in hypertensive rats.