安徽医科大学学报2026,Vol.61Issue(4):644-652,9.DOI:10.19405/j.cnki.issn1000-1492.2026.04.008
敲低TMEM16B减轻大鼠脑缺血再灌注损伤后脑水肿并保护血脑屏障
Knockdown TMEM16B reduces brain edema and protects the blood-brain barrier after cerebral ischemia-reperfusion injury in rats
摘要
Abstract
Objective To explore the effects of transmembrane protein 16B(TMEM16B)on brain edema and blood-brain barrier after cerebral ischemia-reperfusion injury in rats.Methods TMEM16B overexpression and knockdown was performed by adeno-associated virus(AAV),and then adult male Sprague-Dawley rats were sub-jected to middle cerebral artery occlusion(MCAO).Rats were randomly divided into Sham group,MCAO group,AAV no-load group,TMEM16B overexpression group and TMEM16B knockdown group.Modified neurological se-verity scores,adhesive removal test and cylinder test were used to evaluate neurologic function.The ultrastructure of ischemic brain tissue was observed by transmission electron microscope.Brain water content was reflected by dry wet weight ratio of brain tissue.The expressions of TMEM16B,aquaporin4(AQP4),Claudin5 and zonula oc-cludens-1(ZO-1)were investigated by immunofluorescence and Western blot.Results Compared with the AAV no-load group,the sensory and motor functions of rats in TMEM16B overexpression group were significantly im-paired.Mitochondria were swollen;mitochondrial cristae and tight junctions disappeared.The brain water content was higher in overexpression group.The expression of TMEM16B and AQP4 increased while the expression of Claudin5 and ZO-1 decreased(all P<0.05).Compared with the AAV no-load group,the rats in TMEM16B knock-down group showed some recovery in motor function.The mitochondrial cristae and structure were clear,and the basement membrane was partially blurred.The brain water content was lower in knockdown group.The protein lev-els of TMEM16B and AQP4 were lower while the levels of Claudin5 and ZO-1 were higher in TMEM16B knock-down group than in AAV no-load group(all P<0.05).Conclusion An increase in TMEM16B expression aggra-vates brain edema and blood-brain barrier damage in rats after cerebral ischemia-reperfusion injury,while a de-crease in TMEM16B expression alleviates brain edema and protects the blood-brain barrier.关键词
跨膜蛋白16B/脑缺血再灌注损伤/大脑中动脉栓塞模型/脑水肿/血脑屏障/神经保护Key words
transmembrane protein 16B/cerebral ischemia-reperfusion injury/middle cerebral artery occlusion model/brain edema/blood-brain barrier/neuroprotection分类
医药卫生引用本文复制引用
张婧彬,刘倩,潘紫燕,姚天锡,殷姜文..敲低TMEM16B减轻大鼠脑缺血再灌注损伤后脑水肿并保护血脑屏障[J].安徽医科大学学报,2026,61(4):644-652,9.基金项目
国家自然科学基金项目(编号:82160235) National Natural Science Foundation of China(No.82160235) (编号:82160235)