红芪多糖对小鼠糖尿病周围神经病变NGF、NF-kB表达及相关信号通路的影响

Diabetic peripheral neuropathy (DPN) is one of the major complications of diabetic mellitus and the primary cause for crippling of diabetic patients. There are unique advantages of traditional Chinese medicines as therapies for DPN, but the mechanisms are waiting for illumination. What is essential for the oncology and development of DPN is the imbalances between nerve damaging and repairing caused by oxidative stress. Related signaling factors, such as NGF,SCs,NF-KB,Keap1-Nrf2,JNK, play positive role in treating DPN. Our early-stage study shows that HPN is good for DPN in regard of disease prevention and therapy. It functions comprehensively and can balance between nerve damaging and repairing. Signaling pathways related with oxidative stress ,which contributes to nerve damaging, are studied throughout this research. And this research aims at revealing their targets, indexes, and the intercorrelation between different signaling pathways during the evolving of DPN, and additionally, the influence of HPS, yet at different levels, from molecular to cellular and histological levels. This study talks about the mechanism of HPS function during DPN treatment, illuminate the pathology of DPN applying TCM theories, and provide scientific support in DPN prevention and treatment by TCM.

糖尿病周围神经病变（DPN）是糖尿病重要并发症之一，是糖尿病人致残的首要因素。中医药在治疗DPN方面具有独特优势，其科学内涵亟待阐明。氧化应激等因素对神经损伤与抗氧化应激及相关因子对神经保护修复平衡失调处于DPN发生发展的核心地位。NGF、NF-kB表达、SCs凋亡及NF-κB、Keap1-Nrf2、JNK等相关信号通路激活对维持上述平衡及治疗DPN具有重要影响。我们前期研究提示具有“补气、托毒”作用的红芪多糖（HPS）对DPN具有良好的预防和治疗作用，但其作用机制有待进一步探讨。本研究拟选择氧化应激对神经损伤和抗氧化应激对神经保护的重要指标和相关信号通路，通过动物和细胞实验，从组织、细胞和分子学层次观察HPS对DPN发生发展过程中相关指标和信号通路的影响，揭示其作用靶点，探讨其作用机理，阐明DPN病变过程中虚、瘀、毒中医病机理论和机制，为中医药防治DPN提供科学依据。

糖尿病周围神经病变（DPN）是糖尿病重要并发症之一，是糖尿病人致残的首要因素。中医药在治疗DPN方面具有独特优势，其科学内涵亟待阐明。氧化应激等因素对神经损伤与抗氧化应激及相关因子对神经保护修复平衡失调处于DPN发生发展的核心地位。NGF、NF-kB表达、SCs凋亡及NF-κB、Keap1-Nrf2、MAPK等相关信号通路激活对维持上述平衡及治疗DPN具有重要影响。我们前期研究提示具有“补气、托毒”作用的红芪多糖（HPS）对DPN具有良好的预防和治疗作用，但其作用机制有待进一步探讨。本研究以糖尿病周围神经病变ob/ob小鼠和雪旺细胞为研究对象，观察HPS对ob/ob小鼠周围神经神经脱髓鞘病变和高糖培养的雪旺细胞的影响，以及对炎症、氧化应激信号通路Keap1/Nrf2及相关抗氧化酶类的影响。第一阶段研究中发现，HPS可通过上调Nrf2和下调 Keap1蛋白和基因的表达，减轻ob/ob小鼠DPN神经组织纤维化程度，增强机体内抗氧化酶活性。HPS干预治疗均可改善ob/ob小鼠坐骨神经传导速度、改善脱髓鞘病变，在神经组织中可降低NF-κB、IL-1β、高迁率族蛋白1(HMGB1)、Toll样受体4(TLR4)蛋白及mRNA表达，减轻炎症反应导致的神经组织损伤。而第二部分实验以雪旺细胞为研究靶点，进一步验证了红芪多糖改善氧化应激和炎症反应，从而减少雪旺细胞凋亡，最终达到改善糖尿病周围神经脱髓鞘病变。本研选择氧化应激对神经损伤和抗氧化应激对神经保护的重要指标和相关信号通路，通过动物和细胞实验，从组织、细胞和分子学层次观察HPS对DPN发生发展过程中相关指标和信号通路的影响，揭示其作用靶点，探讨其作用机理，阐明DPN病变过程中虚、瘀、毒中医病机理论和机制，揭示中药红芪“补气扶正”作用的科学内涵，为中医药防治DPN提供科学依据。