Apelin-13 对于脑外伤后神经细胞死亡的影响

The Morbidity in the traumatic brain injury (TBI) is 100-150/100000, however,the mortality of TBI is finally up to 30％-50％. And it seriously increases the burden of society. Recently,the mechanism of neuronal cell death subsequent to TBI have been reseached deeply, but the recovery mechanism of neuronal damage after TBI remains elusive. Our subject will utilize a adipokines, Apelin-13,to investigate whether the Apelin-13 involve in the mechanism of rescuing cell death after TBI in vivo or vitro mice TBI model. To testify this original theory, we will utilize the antagonists of necropoptosis, Necrostatin-1 and the antiboby of TNF/Fas. To investigate whether the Apelin-13 rescuing cell death after TBI through autophagy, We also want to use the antagonists and agonists of autophagy. And the behavior deficits were assessed by detecting motor test and Morris water maze. We will examine the levels of autophagy and necropoptosis associate proteins with western-bloting. To conclusion, we will investigate the mechanism of Apelin-13 in rescuing cell death after TBI with various subject methods.And our research may Provid a brand-new therapy methods and drug for TBI.

脑外伤（traumatic brain injury, TBI）发病率约为100～150/10万，死亡率却高达30％～50％,并且其高致残率所造成的社会与医疗护理负担越来越重。目前TBI后神经细胞死亡机制已被深入研究，但TBI后神经细胞自身修复具体机制尚未被了解。本项目利用源于脂肪细胞的因子Apelin-13对TBI后的神经细胞修复机制初步探索。依据我们多年研究的TBI后神经细胞修复机制的经验，利用在体TBI模型和原代培养神经元离体模型，来证明脂肪因子Apelin-13对TBI后神经细胞的修复起到了重要作用这一全新理念，同时应用特异性程序性坏死阻滞剂Necrostatin-1和抗TNF/Fas抗体，自噬的特异性阻断剂和激动剂，应用行为学检测和免疫印迹等方法，从生物化学和功能等方面深入探讨Apelin-13对TBI后神经细胞的保护作用，为临床治疗脑外伤提供崭新的治疗理念和治疗靶点。

脑外伤（traumatic brain injury, TBI）发病率约为100～150/10万，死亡率却高达30％～50％,目前TBI后神经细胞死亡机制虽然已被深入研究，但TBI后神经细胞自身修复具体机制尚未被了解。自噬性细胞死亡（autophagic cell death）也是程序性细胞死亡（programmed cell death，PCD）的一种形式。本项目利用源于脂肪细胞的因子Apelin-13对TBI后的神经细胞修复机制初步探索，利用形态学、蛋白组学、分子生物学和行为学等研究方法，首次证明了（1）Apelin-13对损伤神经细胞起到了保护作用。与盐水组相比，Apelin-13显著地降低了神经细胞死亡数目，脑组织损伤体积，并且极大的促进了记忆功能和运动功能恢复。（2）Apelin-13对脑外伤后神经细胞的自噬产生了抑制，并进一步实验分析这种抑制作用是Apelin-13的保护作用机制之一。（3）Apelin-13对脑外伤后神经细胞的凋亡产生了抑制。研究表明Apelin-13可通过调节Beclin-1/Bcl-2进一步调控自噬与凋亡的发生的机制。揭示证明自噬可能为Apelin-13在脑外伤后起到重要神经保护作用的重要治疗靶点。