研究调控臂丛根性撕脱伤运动神经元凋亡和再生进程的分子机制

In the brachial plexus roots avulsion, our previous studies have demonstrated that the nNOS protein is the crucial factor in motoneurons apoptosis, and the oxidative stress play a role to accerate the death of the motoneurons. Recently, we found that the avulsion-induced changgedd pattern of antioxidative protein ECEL1 and Prx2, lncRNA S69236 and its taged protein Capn2 within the injured motoneurons. by the way, the Calpain2 can proteolyze and active the nNOS protein. So, we hypothesize that the molecular mechanism of "S69236-Calapin2-nNOS/NO,NR2B-Caspase3" plys a role in avulsion-induced motoneurons apoptosis, and "ECEL1-Prx2-ASK-JNK/c-jun,ATF3" might be mechanism for the injured motoneurons survive the avulsion injury. In prensent study, the brachial roots avulsion and reimpantation would be held to build the animal models for motoneurons apoptosis and regeneration,respectively. The transgene mice hSOD1G93A would be used as the animal model for oxidative motoneuron injury. In order to test our hypothesis, the lentivirus carried the gene S69236,Calapin2, ECEL1, or Prx2 would be used to transfect the motoneurons in the injured motoneurons in all of above animal models in vivo. By mediating an over-expression and down-regulation of their RNAs, we will check the expression pattern changes of all of the genes in our hopothesized mechanism. Also, the relations of the intensity of the apoptosis and regenerative motoneurons to the expression patterns of the mentioned genes will be analyzed statistically. This program aim to clarify the molecular mechanism of the avulsion-induced and oxidative stress induced motoneurons death. The results of the the programm will provide the molecular targets for the inhibition of the apoptosis and acceleration of the motor nerve, and also for application of molecular targets on motoneuron neurodegenerative disease.

在臂丛根性撕脱伤,我们发现nNOS蛋白是启动、过氧化损伤是促进运动神经元凋亡的关键,但还不明确调控Nos1基因和过氧化反应的机制。近期我们发现撕脱伤早期运动神经元抗过氧化物ECEL1和Prx2基因、lncRNA S69236及靶Capn2基因均异样表达，而Calpain2能降解激活nNOS蛋白。因此,我们提出:"S69236-Calapin2-nNOS/NO,NR2B-Caspase3"和"ECEL1-Prx2-ASK-JNK/c-jun,ATF3" 分别是运动神经元凋亡和再生的新的分子机制，为验证以上假说，本项目拟用慢病毒转染上述目标基因至大鼠凋亡和再生的运动神经元,同时转染至hSODG93A转基因小鼠过氧化损害的运动神经元，通过研究转染前后上述目标基因的表达及其与神经元凋亡和再生程度的关系，明确创伤运动神经元凋亡和再生的分子机制,得到阻止运动神经元凋亡和促进神经再生的分子靶标。

在臂丛根性撕脱伤,我们发现nNOS蛋白是启动、过氧化损伤是促进运动神经元凋亡的关键,但还不明确调控Nos1基因和过氧化反应的机制。近期我们发现撕脱伤早期运动神经元抗过氧化物ECEL1和Prx2基因、lncRNA S69236及靶Capn2基因均异样表达，而Calpain2能降解激活nNOS蛋白。因此,我们提出:"S69236-Calapin2-nNOS/NO,NR2B-Caspase3"和"ECEL1-Prx2-ASK-JNK/c-jun,ATF3" 分别是运动神经元凋亡和再生的新的分子机制，为验证以上假说，本项目拟用慢病毒转染上述目标基因至大鼠凋亡和再生的运动神经元,同时转染至hSODG93A转基因小鼠过氧化损害的运动神经元，通过研究转染前后上述目标基因的表达及其与神经元凋亡和再生程度的关系，明确创伤运动神经元凋亡和再生的分子机制,得到阻止运动神经元凋亡和促进神经再生的分子靶标。