辅酶CoQ10联合生长抑素II型受体参与神经元可塑性调节在糖尿病周围神经病变中的作用机制研究

糖尿病周围神经病变(DPN)是糖尿病最常见的慢性并发症之一，其发生是长期高血糖及由此导致的代谢障碍、神经营养因子缺乏等多因素联合作用所致。本研究前期发现内源性抗氧化剂辅酶CoQ10能改善DPN诱发的痛觉减退，同时生长抑素II型受体（SSTR2）拮抗剂，对神经病理性疼痛具有致痛作用。据此，本项目拟基于db-/- II型糖尿病小鼠模型，通过外周神经损伤诱发疼痛异常从而建立DPN动物实验模型，观察检测CoQ10处理后小鼠疼痛行为学的变化情况和初级感觉神经元内氧化应激信号通路及相关分子的差异表达情况；明确此过程中神经元可塑性调节机制；通过比较SSTR2特异性拮抗剂联合处理对小鼠疼痛行为学的变化和SSTR2对内源性致痛系统-pERK MAPK信号通路的调控及相关分子的差异表达情况，继而探究CoQ10联合SSTR2参与神经元可塑性调控DPN诱发的痛觉异常的内在机制，为临床诊疗提供新靶标。

Diabetic peripheral neuropathy(DPN) is one of the most common chronic complications of diabetes, which is caused by long-term hyperglycemia and resulting in metabolic disorders, neurotrophic factor deficiency, as so on. In our previous study, we found that endogenous antioxidant coenzyme CoQ10 can improve the symptoms of hypalgesia induced by DPN, and somatostatin type II receptor (SSTR2) antagonist has the hyperalgesia effect after nerve injury. In this project, on the basis of db-/- type II diabetes mouse model, peripheral nerve injury induced experimental DPN animal model; Based on this model, the changes of pain behavior and the expression of oxidative stress signaling pathway and related molecules in primary sensory neuron were observed after CoQ10 treatment; so as to clarify the regulatory mechanism of neuronal plasticity in this process; After the combination of CoQ10 and SSTR2 specific antagonists treatment; comparing the effects of SSTR2 on pain behavior and the regulations of SSTR2 on endogenous pain related pERK pathway in primary sensory neurons and the differential expression of related molecules as well, and then explore the internal mechanism of CoQ10 and SSTR2 involved in neuronal plasticity regulation of DPN induced hyperalgesia and allodynia, so as to provide a new target for clinical treatment.