Inhibition of Endoplasmic Reticulum Stress Preserves the Integrity of Blood-Spinal Cord Barrier in Diabetic Rats Subjected to Spinal Cord Injury.
Inhibition of Endoplasmic Reticulum Stress Preserves the Integrity of Blood-Spinal Cord Barrier in Diabetic Rats Subjected to Spinal Cord Injury.
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抑制内质网应激可保持脊髓损伤的糖尿病大鼠血脊髓屏障的完整性。
DOI：
10.1038/s41598-017-08052-4
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发表时间：
2017-08-09
影响因子：
4.6
通讯作者：
Xiao J
中科院分区：
文献类型：
--
作者：
He Z;Zou S;Yin J;Gao Z;Liu Y;Wu Y;He H;Zhou Y;Wang Q;Li J;Wu F;Xu HZ;Jia X;Xiao J
血脊髓屏障（BSCB）在脊髓损伤（SCI）后的恢复中起着重要作用，糖尿病（DM）损害内皮细胞功能和BSCB的完整性。内质网（ER）应激发生在SCI的早期阶段，并影响预后和细胞存活。然而，ER应激与糖尿病大鼠脊髓损伤后BSCB完整性之间的关系尚不清楚。在这里，我们观察到，糖尿病大鼠表现出增加外渗的伊文思蓝（EB）染料，和损失的内皮细胞和周细胞SCI后1天相比，非糖尿病大鼠。糖尿病也显示出诱导ER应激的激活。在人脑微血管内皮细胞中观察到类似的效果。4-ER应激抑制剂苯基丁酸（4-PBA）降低了糖尿病对SCI的不良影响，减少了EB染料外渗，并限制了内皮细胞和周细胞的损失。此外，4-PBA处理在体内和体外部分逆转了紧密连接和粘附连接的降解。结论：糖尿病可通过诱导内质网应激加重脊髓损伤后BSCB的破坏，而4-PBA抑制内质网应激可能对糖尿病脊髓损伤大鼠BSCB的完整性起有益作用，从而改善预后。
The blood-spinal cord barrier (BSCB) plays significance roles in recovery following spinal cord injury (SCI), and diabetes mellitus (DM) impairs endothelial cell function and integrity of BSCS. Endoplasmic reticulum (ER) stress occurs in the early stages of SCI and affects prognosis and cell survival. However, the relationship between ER stress and the integrity of BSCB in diabetic rats after SCI remains unclear. Here we observed that diabetic rats showed increased extravasation of Evans Blue (EB) dye, and loss of endothelial cells and pericytes 1 day after SCI compared to non-diabetic rats. Diabetes was also shown to induce activation of ER stress. Similar effects were observed in human brain microvascular endothelial cells. 4-phenylbutyric acid (4-PBA), an ER stress inhibitor lowered the adverse effect of diabetes on SCI, reduced EB dye extravasation, and limited the loss of endothelial cells and pericytes. Moreover, 4-PBA treatment partially reversed the degradation of tight junction and adherens junction both in vivo and in vitro. In conclusion, diabetes exacerbates the disruption of BSCB after SCI via inducing ER stress, and inhibition of ER stress by 4-PBA may play a beneficial role on the integrity of BSCB in diabetic SCI rats, leading to improved prognosis.
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影响因子：
6
作者：
Lee, Jee Youn;Choi, Hae Young;Yune, Tae Young
通讯作者：
Yune, Tae Young
影响因子：
4.2
作者：
Kuang, Xianghong;Hu, Wenhui;Yan, Mingshan;Wong, Paul K. Y.
通讯作者：
Wong, Paul K. Y.
影响因子：
14.5
作者：
Lee, Jee Y.;Kim, Hwang S.;Yune, Tae Y.
通讯作者：
Yune, Tae Y.
影响因子：
8.2
作者：
Hawkins, B. T.;Lundeen, T. F.;Egleton, R. D.
通讯作者：
Egleton, R. D.
影响因子：
2.5
作者：
Benton, Richard L.;Maddie, Melissa A.;Whittemore, Scott R.
通讯作者：
Whittemore, Scott R.