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在创伤性脑损伤大鼠模型中,血管内皮生长因子通过基质金属蛋白酶-9调节血脑屏障。

VEGF regulates the blood‑brain barrier through MMP‑9 in a rat model of traumatic brain injury.

作者信息

Wu Muyao, Gong Yating, Jiang Lei, Zhang Min, Gu Haiping, Shen Hui, Dang Baoqi

机构信息

Department of Rehabilitation, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu 215600, P.R. China.

Central Laboratory, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu 215600, P.R. China.

出版信息

Exp Ther Med. 2022 Oct 24;24(6):728. doi: 10.3892/etm.2022.11664. eCollection 2022 Dec.

Abstract

Blood-brain barrier (BBB) damage is closely related to morbidity and mortality in patients with traumatic brain injury (TBI). Inhibition of VEGF effectively protects BBB integrity in clinical ischemic stroke. Protecting BBB integrity, reducing brain edema and alleviating post-TBI secondary brain injury are key to a favorable patient prognosis. MMP-9 affects BBB integrity by destroying the tight junction of vascular endothelial cells and inhibiting the transport and enzymatic systems. The present study aimed to examine the possible interplay between VEGF and MMP-9 in TBI. A TBI model was established in 87 male Sprague-Dawley rats. Reverse transcription-quantitative PCR, western blotting, wet-dry brain edema assessment, TUNEL and Fluoro-Jade C staining were performed to analyze the brain tissue samples of the rats. The results showed that compared with in the Sham group rats, the mRNA and protein expression levels of VEGF and MMP-9 were increased at 24 h post-TBI. After bevacizumab treatment, BBB permeability and nerve cell apoptosis were markedly reduced. In conclusion, the present study revealed a potential role for TBI-associated VEGF and MMP-9 upregulation in BBB disruption and nerve damage post-TBI.

摘要

血脑屏障(BBB)损伤与创伤性脑损伤(TBI)患者的发病率和死亡率密切相关。在临床缺血性卒中中,抑制血管内皮生长因子(VEGF)可有效保护血脑屏障的完整性。保护血脑屏障的完整性、减轻脑水肿以及缓解TBI后的继发性脑损伤是患者获得良好预后的关键。基质金属蛋白酶-9(MMP-9)通过破坏血管内皮细胞的紧密连接以及抑制转运和酶系统来影响血脑屏障的完整性。本研究旨在探讨VEGF与MMP-9在TBI中可能的相互作用。在87只雄性Sprague-Dawley大鼠中建立TBI模型。采用逆转录定量PCR、蛋白质印迹法、干湿法脑水肿评估、TUNEL法以及荧光金C染色对大鼠脑组织样本进行分析。结果显示,与假手术组大鼠相比,TBI后24小时VEGF和MMP-9的mRNA和蛋白表达水平升高。贝伐单抗治疗后,血脑屏障通透性和神经细胞凋亡明显降低。总之,本研究揭示了TBI相关的VEGF和MMP-9上调在TBI后血脑屏障破坏和神经损伤中的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/710b/9634340/0821726ede98/etm-24-06-11664-g00.jpg

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