XPD修复酶在糖尿病加重局麻药神经毒性作用中的机制研究

糖尿病患者接受神经阻滞麻醉或镇痛后，发生或加重神经损伤的风险可明显增加；高糖环境不利于局麻药所致正常神经元损伤的修复，但其分子机制尚不明确。本科研小组前期发现局麻药可使神经细胞的XPD修复酶表达水平增加，而神经细胞在高糖环境下XPD修复酶水平明显下降。我们推测：该分子机制可能与高糖环境使XPD修复酶水平降低，导致局麻药引发神经损伤的DNA修复受到抑制有关。本研究拟应用多种分子生物学技术，探讨局麻药及高糖环境对神经细胞的XPD水平及DNA损伤的影响；构建XPD高表达及低表达细胞株，并在体内试验中建立XPD基因敲除小鼠模型，研究XPD在局麻药及高糖环境下对神经细胞的保护作用，以揭示高糖对局麻药引发神经损伤病变的作用及机制。本研究为如何防治糖尿病或血糖偏高病人应用局麻药后神经病变加重及减少患者神经损伤的发生提供理论依据。

Previous studies have reported that the risk of nerve injury in diabetic patients may increase after the treatment of nerve block anesthesia or analgesia, high glucose goes against neuronal regeneration after injury caused by local anesthetics, However, the molecular mechanism involved it is still unclear. We previously found XPD repair enzyme of nerve cells increased following the local anesthetics treatment, but decreased in the high glucose conditions. We hypothesize that reduced XPD repair enzyme caused by high glucose inhibits the DNA repair system of induced by local anesthetics. In order to reveal the effect and mechanisms of nerve damage caused by local anesthics in high glucose conditions. In this study, we will use different molecular biological techniques to investigate the level of XPD and DNA damage affected by local anesthetics and high glucose conditions. We will constructed cells with overexpression and down-regulated XPD gene and use the XPD gene knockout mice to study the protective effect of XPD in nerve repair system following the treatments of local anethetics and high glucose conditions. This study will lays a theoretical foundation on how to avoid and control nerve damage in diabetes or high blood sugar patients after local anesthetics treatment.