HSPA12B对感染性休克内皮功能不全的保护作用及机制研究：对MEK/ERK/NF-κB炎症信号的负调节

Heat shock protein A12B (HSPA12B) is the newest member of HSP70 family and is specifically expressed in vascular endothelial cells. However, little is known about the effects of HSPA12B on endothelial function in septic shock. Our preliminary experiment showed that overexpression of HSPA12B was associated with endothelial protection in lipopolysaccharide-induced septic shock, but its mechanism remains unknown. Therefore, we hypothesized that overexpression of HSPA12B may reduce the systemic inflammatory response and protect organ function by inhibiting the activity of the MEK/ERK signaling pathway in septic shock. In our study, the protective effects of HSPA12B on endothelial function in septic shock will be studied by RT-PCR, Western-Blot, adenovirus vector transfection and RNA interference methods in vivo and in vitro. Finally, our results will provide new approach for the prevention and treatment of septic shock and its complications by using HSPA12B.

HSPA12B是热休克蛋白70家族中最新成员，也是特异性表达于血管内皮细胞的热休克蛋白。迄今对HSPA12B与感染性休克后内皮功能的关系知之甚少。我们预实验结果提示HSPA12B可以改善感染性休克小鼠内皮功能不全，但其作用机制还有待进一步探讨。为此，我们提出假设：高表达的HSPA12B可能通过抑制MEK/ERK信号通路活性，改善感染性休克内皮功能的紊乱，从而减轻全身炎症反应，保护器官功能。为了验证这一假设，我们将通过HSPA12B转基因鼠和基因敲除鼠、原代人脐静脉内皮细胞，采用RT-PCR、Western-Blot、腺病毒载体转染、RNA干扰等手段，从分子、细胞、组织以及动物整体水平多方面探讨HSPA12B改善感染性休克内皮功能的损害，明确HSPA12B通过抑制MEK/ERK信号通路活性保护内皮功能。本研究将从HSPA12B对内皮功能的保护这个新视点为感染性休克及其并发症的防治提供新思路。

热休克蛋白A12B（HSPA12B）是热休克蛋白70家族中最新成员，也是特异性表达于血管内皮细胞的热休克蛋白。迄今对HSPA12B与感染性休克后内皮功能的关系知之甚少。我们以人脐静脉内皮细胞为研究对象，通过构建高表达和低表达HSPA12B的人脐静脉内皮细胞模型，用细菌脂多糖对其刺激，采用RT-PCR、Western-Blot、腺病毒载体转染、RNA干扰等手段，通过测定细胞的通透性、细胞粘附、细胞迁移能力、炎症因子的表达等指标，结果发现高表达的HSPA12B通过激活PI3K/Akt信号通路改善感染性休克内皮功能的损害。本研究从HSPA12B对内皮功能的保护这个新视点为感染性休克及其并发症的防治提供了新思路。