Abstract:
Cerebral ischemia is a common neurodegenerative disease in which damage to the blood-brain barrier (BBB) is the main consequence. In cerebral ischemia, the level of miR-149-5p and tight junction proteins are decreased, while the level of Calpine is increased, finally leading to increased BBB permeability. This study investigated the effect of miR-149-5p mimic on the expression of Calpain, Occludin, and ZO-1 and the consequences of cerebral ischemia. Cerebral ischemia model was performed via middle cerebral artery occlusion (MCAO) method on female Wistar rats. Four groups of Wistar rats were studied: Sham, cerebral ischemia without treatment, Scramble miR, and miR-149-5p mimic treatment. Then, neurological defects and BBB permeability (via Evans blue staining), cerebral edema (cerebrospinal fluid percentage), and ZO-1, Occludin, and Calapin expression (by quantitative real time- PCR) were investigated. qRT-PCR results showed miR-149-5p expression decreases after cerebral ischemia induction. In addition, Occludin and ZO-1 expression significantly increased in miR-149-5p group. In contrast, Calapin expression, BBB permeability, brain water content and neurological defects were significantly decreased. It seems that the increased level of miR-149-5p exerts its protective effect on cerebral ischemia due to increasing of tight junction proteins.
摘要:
脑缺血是一种常见的神经退行性疾病,其主要后果是血脑屏障(BBB)受损。在脑缺血中,miR-149-5p和紧密连接蛋白的水平降低,当Calpine的水平增加时,最终导致BBB通透性增加。这项研究调查了miR-149-5p模拟物对Calpain表达的影响,Occludin,和ZO-1和脑缺血的后果。采用大脑中动脉阻断法(MCAO)建立雌性Wistar大鼠脑缺血模型。研究了四组Wistar大鼠:假,脑缺血未经治疗,争夺miR,和miR-149-5p模拟治疗。然后,神经缺陷和血脑屏障通透性(通过伊文思蓝染色),脑水肿(脑脊液百分比),和ZO-1,Occludin,和Calapin表达(通过定量实时PCR)进行研究。qRT-PCR结果显示miR-149-5p在脑缺血诱导后表达降低。此外,miR-149-5p组中Occludin和ZO-1表达显著增加。相比之下,Calapin表达式,BBB通透性,脑含水量和神经系统缺陷明显下降。似乎miR-149-5p水平的增加由于紧密连接蛋白的增加而对脑缺血发挥其保护作用。