基于IRE1/NF-κB通路的丹皮萜苷组分调控肾系膜微炎症作用及机制研究

项目名称： 基于IRE1/NF-κB通路的丹皮萜苷组分调控肾系膜微炎症作用及机制研究

项目编号： No.81503314

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张明华

作者单位： 南京中医药大学

项目金额： 18万元

中文摘要： 内质网应激(ERS)失衡是糖尿病肾病(DN)系膜细胞损伤早期微炎症反应的重要机制之一。 IRE1/NF-κB通路是该机制最为敏感的干预靶标之一。我们前期研究提示牡丹皮萜苷组分可能通过调控ERS失衡减轻系膜微炎症反应，但作用机制不明确。本项目在前期研究基础上，以“丹皮萜苷组分调控肾系膜ERS失衡所致的微炎症作用可能与IRE1/NF-κB通路密切相关”为科学假说，采用AGEs诱导HBZY-1肾系膜细胞的微炎症模型和STZ诱导的DN小鼠模型，借助siRNA等技术特异性干预IRE1/NF-κB，研究丹皮萜苷组分调控系膜ERS失衡所致的微炎症作用特点与分子机制，验证其对IRE1/NF-κB通路的作用特点，揭示其潜在作用机制和靶标。本项目创新地从微炎症和ERS失衡角度研究丹皮萜苷组分调控肾系膜病理的作用机制，对于深入理解丹皮防治 DN机制和推动靶向干预DN的创新药物研发具有重要理论和实际意义。

中文关键词： 糖尿病肾病；内质网应激；牡丹皮；微炎症；IRE1/NF-κB；通路

英文摘要： The imbalance of endoplasmic reticulum stress (ERS) is one of the important mechanisms of microinflammatory response in mesangial cell early damage of diabetic nephropathy (DN). Studies demonstrated that IRE1/NF-κB pathway is one of the most sensitive targets of the intervention mechanism. Our preliminary research suggested that the terpene glycoside component of Mudanpi might reduce mesangial microinflammation response through regulating ERS imbalance, however, the underlying mechanism is still unknown. Based on our preliminary studies, we proposed a scientific hypothesis on “Regulatory of terpene glycoside of Mudanpi on glomeruli mesangial micro-inflammation caused by ERS imbalance may be associated with IRE1/NF-κB pathway”. This project intends to adopt AGEs-induced mesangial HBZY-1 cell microinflammatory model and STZ-induced DN mice model, uses siRNA and other techniques to intervene specifically IRE1/NF-κB pathway, reveals the regulation features and molecular mechanism of terpene glycoside component of Mudanpi on ERS imbalance-mediated glomeruli mesangial microinflammation, and to verify its action characteristics for JNK/AP1 and IKK/IκB signaling events in IRE1/NF-κB pathway, and finally reveal its underlying mechanisms and targets. This research project investigates innovatively the mechanism of terpene glycoside component of Mudanpi on regulating glomeruli mesangial pathology from microinflammation and endoplasmic reticulum stress imbalance, and it has an important theoretical and practical significance in depth understanding for the prevention and treatment mechanism of Mudanpi on DN pathological lesions and promoting the development of innovative drugs for targeting interventions for DN.

英文关键词： Diabetic nephropathy;endoplasmic reticulum stress;Mudanpi;microinflammatory;IRE1/NF-κB pathway