miR-539 Targeting SNAI2 Regulates MMP9 Signaling Pathway and Affects Blood-Brain Barrier Permeability in Cerebrovascular Occlusive Diseases: A Study Based on Head and Neck Ultrasound and CTA

This study aimed to explore the expression level of miR-539 in the blood-brain barrier permeability induced by cerebrovascular occlusion and its mediated mechanism. Altogether, 48 patients with cerebral vascular occlusion lesions from March 2018 to June 2020 were collected. The expression level of miR-539 in the peripheral blood serum of the subjects was analyzed by qRT-PCR, and the participants were divided into two groups according to the results of head and neck ultrasound and CTA hemodynamics. The MCAO model of cerebral ischemia was established in rats, and the expression level of miR-539 was detected by qRT-PCR in brain tissues of different groups of rats. The effects of miR-539 on the permeability of blood-brain barrier were investigated by intraventricular injection of agomiR-539 and antagomir-539. The model of blood-brain barrier was established by culturing brain microvascular endothelial cells and pericytes in vitro, and the changes of miR-539 expression level and permeability after glucose and oxygen deprivation were detected. The expression level of SNAI2/MMP9 signaling pathway protein in cells was detected by Western blot. Compared with the healthy control group, the expression level of miR-539 in peripheral blood of patients with cerebrovascular occlusive disease decreased significantly, and the expression level of miR-539 in the MCAO rat model decreased and affected the permeability of blood-brain barrier. Glucose and oxygen deprivation treatment in brain microvascular endothelial cells can lead to downregulation of miR-539 expression and affect cell permeability. miR-539 in brain microvascular endothelial cells can target and bind to SNAI2 and participate in the regulation of endothelial cell permeability by affecting the SNAI2/MMP9 signaling pathway. The results of this study suggested that circulating miR-539 in peripheral blood may be a potential marker for predicting blood-brain barrier permeability after ischemic stroke. More detailed studies are needed to determine its diagnostic value.