Soluble epoxide hydrolase inhibitor protects against blood-brain barrier dysfunction in a mouse model of type 2 diabetes via the AMPK/HO-1 pathway

被引：17

作者：

Wu, Jing ^{[1
]}

Zhao, Yuxing ^{[1
]}

Fan, Zhen ^{[1
]}

Chen, Qiunan ^{[1
]}

Chen, Jinliang ^{[1
]}

Sun, Yue ^{[1
]}

Jiang, Xushun ^{[2
]}

Xiao, Qian ^{[1
]}

机构：

[1] Chongqing Med Univ, Dept Geriatr, Affiliated Hosp 1, Friendship Rd 1, Chongqing 400016, Peoples R China

[2] Chongqing Med Univ, Dept Nephrol, Affiliated Hosp 1, Friendship Rd 1, Chongqing 400016, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2020年 / 524卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Diabetes; sEH inhibitor; Blood-brain barrier; ROS; AMPK; HO-1; PROMOTES MITOCHONDRIAL BIOGENESIS; HYPERGLYCEMIA; ENDOTHELIUM; ACTIVATION;

D O I：

10.1016/j.bbrc.2020.01.085

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Diabetes mellitus is a metabolic disorder that can lead to blood-brain barrier (BBB) disruption and cognitive decline. However, the mechanisms of BBB breakdown in diabetes are still unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects on vascular structure and functions. In the current study, we showed increased vascular permeability of the BBB, which was accompanied by upregulation of sEH and downregulation of 14,15-EET. Moreover, the sEH inhibitor t-AUCB restored diabetic BBB integrity in vivo, and 14,15-EET prevented ROS accumulation and MEC injury in vitro. t-AUCB or 14,15-EET treatment provoked AMPK/HO-1 activation under diabetic conditions in vivo and in vitro. Thus, we suggest that decreased EET degradation by sEH inhibition might be a potential therapeutic approach to attenuate the progression of BBB injury in diabetic mice via AMPK/HO-1 pathway activation. (C) 2020 Elsevier Inc. All rights reserved.

引用

页码：354 / 359

页数：6

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