Hydrogen Sulfide Ameliorates Blood-Spinal Cord Barrier Disruption and Improves Functional Recovery by Inhibiting Endoplasmic Reticulum Stress-Dependent Autophagy.
Hydrogen Sulfide Ameliorates Blood-Spinal Cord Barrier Disruption and Improves Functional Recovery by Inhibiting Endoplasmic Reticulum Stress-Dependent Autophagy.
复制标题
硫化氢通过抑制内质网应激依赖性自噬来改善血液-脊髓屏障破坏并改善功能恢复。
DOI：
10.3389/fphar.2018.00858
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发表时间：
2018
影响因子：
5.6
通讯作者：
Xiao J
中科院分区：
文献类型：
--
作者：
Wang H;Wu Y;Han W;Li J;Xu K;Li Z;Wang Q;Xu K;Liu Y;Xie L;Wu J;He H;Xu H;Xiao J
脊髓损伤（SCI）引起血脊髓屏障（BSCB）的破坏，通过引发继发性损伤引起神经功能障碍。硫化氢（H2S）是一种气体介质，据报道在中枢神经系统中具有神经保护作用。然而，SCI期间H2S与BSCB破坏之间的关系尚不清楚。因此，评估NaHS （H2S供体）是否可以保护BSCB免受SCI侵害并研究其潜在机制是很有趣的。在本研究中，我们发现脊髓损伤在T9水平显著激活大鼠脊髓完全碾压损伤模型的内质网应激和自噬。NaHS处理在体内和体外均可防止紧密连接（TJ）和粘附连接（AJ）蛋白的丢失。然而，内质网应激激活剂（tunicamycin， TM）和自噬激活剂（rapamycin, Rapa）显著降低了NaHS对BSCB恢复的保护作用。此外，内质网应激抑制剂（4-苯基丁酸，4-PBA）显著阻断了sci诱导的自噬。而自噬抑制剂（3-甲基腺嘌呤，3-MA）仅抑制自噬，对内质网应激无明显影响。最后，我们发现NaHS可显著减轻脊髓损伤后BSCB的通透性，改善脊髓损伤后的功能恢复，而TM和Rapa可显著逆转这些作用。综上所述，我们的研究表明，NaHS治疗有利于脊髓损伤的恢复，表明H2S治疗是一种潜在的促进脊髓损伤恢复的治疗策略。
Spinal cord injury (SCI) induces the disruption of blood-spinal cord barrier (BSCB), which elicits neurological deficits by triggering secondary injuries. Hydrogen sulfide (H2S) is a gaseous mediator that has been reported to have neuroprotective effect in the central nervous system. However, the relationship between H2S and BSCB disruption during SCI remains unknown. Therefore, it is interesting to evaluate whether the administration of NaHS, a H2S donor, can protect BSCB integrity against SCI and investigate the potential mechanisms underlying it. In present study, we found that SCI markedly activated endoplasmic reticulum (ER) stress and autophagy in a rat model of complete crushing injury to the spinal cord at T9 level. NaHS treatment prevented the loss of tight junction (TJ) and adherens junction (AJ) proteins both in vivo and in vitro. However, the protective effect of NaHS on BSCB restoration was significantly reduced by an ER stress activator (tunicamycin, TM) and an autophagy activator (rapamycin, Rapa). Moreover, SCI-induced autophagy was remarkably blocked by the ER stress inhibitor (4-phenylbutyric acid, 4-PBA). But the autophagy inhibitor (3-Methyladenine, 3-MA) only inhibited autophagy without obvious effects on ER stress. Finally, we had revealed that NaHS significantly alleviated BSCB permeability and improved functional recovery after SCI, and these effects were markedly reversed by TM and Rapa. In conclusion, our present study has demonstrated that NaHS treatment is beneficial for SCI recovery, indicating that H2S treatment is a potential therapeutic strategy for promoting SCI recovery.
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影响因子：
20.1
作者：
Calvert JW;Jha S;Gundewar S;Elrod JW;Ramachandran A;Pattillo CB;Kevil CG;Lefer DJ
通讯作者：
Lefer DJ
Netrin-1 在大鼠脊髓损伤后通过自噬刺激改善功能恢复的作用。
影响因子：
5.3
作者：
Bai L;Mei X;Wang Y;Yuan Y;Bi Y;Li G;Wang H;Yan P;Lv G
通讯作者：
Lv G
影响因子：
3.7
作者：
Chandrika BB;Yang C;Ou Y;Feng X;Muhoza D;Holmes AF;Theus S;Deshmukh S;Haun RS;Kaushal GP
通讯作者：
Kaushal GP
升高的 microRNA-129-5p 水平可通过抑制 HMGB1 和 TLR3 细胞因子途径改善缺血再灌注后的神经炎症和血脊髓屏障损伤。
影响因子：
9.3
作者：
Li XQ;Chen FS;Tan WF;Fang B;Zhang ZL;Ma H
通讯作者：
Ma H
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.