Propofol Protects Against TNF-α-induced Blood-brain Barrier Disruption via the PIM-1/eNOS/NO Pathway

被引：16

作者：

Lu, Yan ^{[1
]}

Xu, Zhendong ^{[1
]}

Shen, Fuyi ^{[1
]}

Lin, Rong ^{[1
]}

Li, Haibing ^{[1
]}

Lv, Xiang ^{[2
]}

Liu, Zhiqiang ^{[1
]}

机构：

[1] Tongji Univ, Shanghai First Matern & Infant Hosp, Dept Anesthesiol, Sch Med, Shanghai 201204, Peoples R China

[2] Shanghai Jiao Tong Univ, Dept Anesthesiol & Crit Care Med, Sch Med, Shanghai Peopoles Hosp 9, Shanghai, Peoples R China

来源：

CURRENT NEUROVASCULAR RESEARCH | 2020年 / 17卷 / 04期

关键词：

Propofol; blood-brain barrier; postoperative cognitive dysfunction; TNF-alpha; interleukin; endothelial cells; POSTOPERATIVE COGNITIVE DYSFUNCTION;

D O I：

10.2174/1567202617999200819142021

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

Background: The Inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), disrupts blood-brain barrier (BBB). Propofol reportedly exerts an anti-inflammatory effect in the central nervous system. Objective: We hypothesized that propofol could provide a protective effect against TNF-alpha-induced disruption in human cerebral microvascular endothelial cells (hCMEC/D3 cells) and explored the underlying mechanisms. Methods: The hCMEC/D3 cell monolayers were pretreated with propofol, followed by TNF-alpha treatment. The integrity of BBB was reflected by assessing the trans-endothelial electrical resistance (TEER) and determining the expression of proteins within tight junctions (TJs). The effect of propofol on TNF-alpha-modulated nitric oxide production was measured by a nitrate reductase assay kit. The expression of ZO-1, claudin-5, occludin, TNF receptor 1 (TNFR1), TNF receptor 2 (TNFR2), proviral-integration site for Moloney murine leukaemia virus (PIM)-1Icinase, the phosphorylation of endothelial nitric oxide synthase at ser(6)(33) (peNOS-ser(6)(33)) were detected by western blot. Results: In hCMEC/D3 cells, TNF-alpha treatment markedly disrupted the integrity of BBB. Further, we found TNF-alpha treatment could increase the expression of PIM-1, then activate the phosphorylation of eNOS and induce the release of nitric oxide (NO). More importantly, we found that TNF-alpha-impaired BBB integrity could be reversed by propofol. Conclusion: These results suggest that the PIM-1/eNOS/NO pathway plays a vital role, in which Propofol protects against TNF-alpha-induced blood-brain barrier disruption.

引用

页码：471 / 479

页数：9

共 40 条

[1]

Cannabidiol Enhances the Passage of Lipid Nanocapsules across the Blood-Brain Barrier Both in Vitro and in Vivo [J].