a7nAchR对心肺复苏鼠脑损伤的保护作用及其机制研究

Cerebral damage is the most important factor that constraints the life quality in patients after cardiopulmonary resuscitation. So far we have known less about the pathogenesis of the brain damage post-CPR and lack of effective treatment. The results of our preliminary experiment suggest that α7nAchR play an important role in the protection of cardiac function after CPR. However, its role and mechanisms in cerebral injury are to be further investigated. So we put forward the hypothesis: α7nAchR may play a protective role in the cerebral damage after CPR through neural anti-inflammatory mechanism. To test this hypothesis and clarify the mechanism of α7nAchR on cerebral damage after CPR, we will dynamically observe the secretion of Ach mRNA by CPR model on gene knockout rats and methods of RT-PCR, Western blots. We will also observe the changes of NF-κB expression and brain cells apoptosis that due to α7nAchR changes by α7nAchR agonists on C57BL/6J gene knockout rats. At the same time, we will monitor the rat mortality and electron microscopy of brain tissue. From this new point of neural anti-inflammatory mechanism of α7nAchR, this study will provide new ideas for pathogenesis, prevention and treatment on brain injury after CPR.

脑功能损害是制约心肺复苏患者复苏后生存质量的最主要因素，迄今对复苏后脑损伤的发病机制知之甚少且缺乏有效的治疗方法。我们近期的实验结果提示，α7烟碱型胆碱能神经受体（α7nAchR）在复苏后心功能保护中发挥重要的作用，但其在脑损伤中的作用及机制有待进一步探讨。为此，我们提出假说：α7nAchR可能通过神经抗炎机制在复苏后脑损伤中发挥保护作用。为验证这一假说，本项目通过基因敲除大鼠心肺复苏模型，利用RT-PCR、Western blots等方法动态观察Ach mRNA的分泌情况，通过α7nAchR激动剂和遗传背景为C57BL/6J的基因敲除大鼠观察α7nAchR变化对NF-κB表达、脑细胞凋亡的影响，并监测大鼠死亡率和脑组织电镜检查，明确α7nAchR在复苏后脑损伤中的作用机制。本研究将从α7nAchR的神经抗炎机制这个新视点为揭示复苏后脑损伤的发生机制奠定基础，为脑损伤的防治提供新的思路。