HSPA12B promotes functional recovery after ischaemic stroke through an eNOS-dependent mechanism.
HSPA12B promotes functional recovery after ischaemic stroke through an eNOS-dependent mechanism.
复制标题
HSPA12B 通过 eNOS 依赖性机制促进缺血性中风后的功能恢复。
DOI：
10.1111/jcmm.13507
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发表时间：
2018-04
影响因子：
5.3
通讯作者：
Ding Z
中科院分区：
文献类型：
--
作者：
Zhao Y;Liu C;Liu J;Kong Q;Mao Y;Cheng H;Li N;Zhang X;Li C;Li Y;Liu L;Ding Z
中风是全世界残疾的主要原因。 HSPA12B 是一种热休克蛋白，最近发现在内皮细胞中特异性表达，能够促进血管生成。在这里，我们研究了它对缺血性中风慢性期功能恢复的影响。 60分钟诱发缺血性中风。 HSPA12B (HSPA12B Tg) 过度表达的转基因小鼠和野生型同窝小鼠 (WT) 中大脑中动脉闭塞的影响。 HSPA12B Tg 小鼠在中风后 28 天内表现出比 WT 小鼠显着更高的存活率。在中风后 21 天内，与 WT 对照小鼠相比，HSPA12B Tg 小鼠的神经功能显着改善，自发运动活动增加，焦虑减少。在中风后第 28 天检查的 HSPA12B Tg 小鼠中，中风引起的海马变性减弱。有趣的是，与 WT 小鼠相比，HSPA12B Tg 小鼠的梗塞周围血管生成（中风后 28 天检查）和海马神经发生（中风后 7 天检查）分别增强。 HSPA12B Tg 小鼠中中风诱导的 eNOS 磷酸化和 TGF-β1 表达增强。然而，给予 eNOS 抑制剂 L-NAME 会减弱 HSPA12B 诱导的神经功能恢复和中风后小鼠存活的保护作用。数据表明，HSPA12B 通过 eNOS 依赖性机制促进中风后的功能恢复和生存。靶向 HSPA12B 表达可能对中风引起的功能障碍和死亡具有治疗潜力。
Stroke is the leading cause of disability worldwide. HSPA12B, a heat‐shock protein recently identified expression specifically in endothelial cells, is able to promote angiogenesis. Here, we have investigated its effects on functional recovery at chronic phase of ischaemic stroke. Ischaemic stroke was induced by 60 min. of middle cerebral artery occlusion in transgenic mice with overexpression of HSPA12B (HSPA12B Tg) and wild‐type littermates (WT). HSPA12B Tg mice demonstrated a significant higher survival rate than WT mice within 28 days post‐stroke. Significant improved neurological functions, increased spontaneous locomotor activity and decreased anxiety were detected in HSPA12B Tg mice compared with WT controls within 21 days post‐stroke. Stroke‐induced hippocampal degeneration was attenuated in HSPA12B Tg mice examined at day 28 post‐stroke. Interestingly, HSPA12B Tg mice showed enhanced peri‐infarct angiogenesis (examined 28 days post‐stroke) and hippocampal neurogenesis (examined 7 days post‐stroke), respectively, compared to WT mice. The stroke‐induced eNOS phosphorylation and TGF‐β1 expression were augmented in HSPA12B Tg mice. However, administration with eNOS inhibitor L‐NAME diminished the HSPA12B‐induced protection in neurological functional recovery and mice survival post‐stroke. The data suggest that HSPA12B promoted functional recovery and survival after stroke in an eNOS‐dependent mechanism. Targeting HSPA12B expression may have a therapeutic potential for the stroke‐evoked functional disability and mortality.
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影响因子：
2.7
作者：
Crawford, Cynthia A.;Der-Ghazarian, Taleen;Britt, Cynthia E.;Varela, Fausto A.;Kozanian, Olga O.
通讯作者：
Kozanian, Olga O.
影响因子：
8.3
作者：
Ergul A;Alhusban A;Fagan SC
通讯作者：
Fagan SC
影响因子：
5.3
作者：
Ohab, John J.;Fleming, Sheila;Carmichael, S. Thomas
通讯作者：
Carmichael, S. Thomas
影响因子：
8.3
作者：
KRUPINSKI, J;KALUZA, J;WANG, JM
通讯作者：
WANG, JM
DOI：
10.1161/atvbaha.111.237263
发表时间：
2012-01-01
影响因子：
8.7
作者：
Fujimura, Noritaka;Jitsuiki, Daisuke;Higashi, Yukihito
通讯作者：
Higashi, Yukihito