基于氧化应激诱导细胞凋亡探讨糖痹康促糖尿病周围神经修复作用机制研究

Diabetic peripheral neuropathy (DPN) treatment is medical research hot spot and the difficulty, at present, the western medicine lack of effective means alleiating DPN, the treatment of traditional Chinese medicine for DPN accumulated rich experience, the curative effect is accurate, but mechanism to be clarified. .Oxidative stress is one of DPN pathological mechanism, DPN cell apoptosis is an important form of nerve damage when, schwann cells (SCs) in the nerve damage repair after plays a key role. This subject is based on the previous studies in "oxidatie stress causes the cell apoptosis" as the breakthrough point, taking the classical p38MAPK, Wnt/beta catenin signal pathway as the main line, through the whole from the body and experiment, is used to RT-PCR, Wester blot, confocal laser scanning electron microscope (sem), and other methods, the further observation Tangbikang certified STZ-DM to Cornwall rat oxidatie stress, and the cell apoptosis and in vitro high sugar rats induced apoptosis and signal transduction pathways SCs, the effects of Tangbikang to explore more kang high sugar environment cause oxidative stress, and oxidative stress lead to the influence of the cell apoptosis, plans from the overall and a cellular level to explore more sugar Cornwall DPN nerve to protect the role of the possible mechanism, clinical medicine for provide theoretical and experimental basis, for to improve mental derangement become targets of the new drug development to explore new ways.

糖尿病周围神经病变（DPN）的治疗是医学研究的热点和难点，目前西药治疗DPN尚缺乏有效手段，而中医药治疗DPN积累了丰富经验，疗效确切，但作用机制亟待阐明。氧化应激是DPN主要病理机制之一，细胞凋亡是DPN时神经损伤的重要形式，雪旺细胞（SCs）在神经损伤后修复中起着关键性作用。本课题在前期研究基础上以"氧化应激导致细胞凋亡"为切入点，以p38MAPK信号通路为主线，通过整体和离体实验，拟采用RT-PCR、Wester blot、免疫组化、扫描电镜等方法，进一步观察糖痹康对STZ-DM大鼠氧化应激导致细胞凋亡和体外高糖诱导大鼠SCs凋亡信号转导通路的影响，探讨糖痹康对高糖环境诱发氧化应激，以及氧化应激导致细胞凋亡的影响，拟从整体和细胞水平探讨糖痹康对DPN神经保护作用的可能机制，为临床用药提供理论和实验依据，为以改善神经病变为靶点的新药研发探索新途径。

糖尿病周围神经病变（DPN）的治疗是医学研究的热点和难点，目前西药治疗DPN尚缺乏有效手段，而中医药治疗DPN积累了丰富经验，疗效确切，但作用机制亟待阐明。氧化应激是DPN主要病理机制之一，细胞凋亡是DPN时神经损伤的重要形式，雪旺细胞（SCs）在神经损伤后修复中起着关键性作用。本课题在前期研究基础上以“氧化应激导致细胞凋亡”为切入点，以经典的p38MAPK、Wnt/β-catenin信号通路为主线，通过整体和离体实验，拟采用RT-PCR、Wester blot、免疫组化等方法，进一步观察糖痹康对STZ-DM大鼠氧化应激导致细胞凋亡和体外高糖诱导大鼠SCs凋亡及信号转导通路的影响。结果显示糖痹康能够改善糖尿病大鼠坐骨神经传导速度，促进坐骨神经IGF-1和IGF-1R蛋白表达，抑制NADPH氧化酶Phox p22亚基、iNOS、Caspase-3蛋白和基因表达，促进抑制凋亡Bcl-2蛋白和基因表达。糖痹康能够抑制高糖环境下雪旺细胞凋亡，上调β-catenin、Bcl-2因子表达，抑制p38MAPK、Caspase-3因子表达。提示糖尿病调节p38MAPK、Wnt/β-catenin信号通路可能是其防治糖尿病周围神经病变的作用机制，为临床用药提供理论和实验依据，为以改善神经病变为靶点的新药研发探索新途径。