雷公藤多苷联合小檗碱预防和治疗2型糖尿病肾小管间质病变的作用机制研究

项目名称： 雷公藤多苷联合小檗碱预防和治疗2型糖尿病肾小管间质病变的作用机制研究

项目编号： No.81470187

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 陈莉明

作者单位： 天津医科大学

项目金额： 72万元

中文摘要： 肾小管间质病变以炎性细胞浸润、细胞因子表达失调、细胞外基质沉积为特征，炎性细胞浸润和肾小管上皮细胞转分化是其中心环节。高糖状态下肾小管TLR4表达增加，进而激活NF-KB，促进肾间质炎症的进展。TLR4/NF-κB通路在肾小管间质病变中可能起重要作用。前期研究发现：雷公藤多甙能抑制促炎细胞因子产生，减轻肾脏局部炎症，雷公藤多甙联合小檗碱在改善糖尿病大鼠肾小球硬化的同时，能减轻肾小管间质病变。据此我们提出雷公藤多甙联合小檗碱通过抑制TLR4/NF-κB炎症通路延缓糖尿病肾病肾小管间质病变的假说。本研究以自发2型糖尿病大鼠和肾小管上皮细胞为研究对象，以TLR4/NF-κB炎症通路及Smads通路为切入点，通过光镜、电镜、免疫组化、RT-PCR、Western blot等方法探讨雷公藤多甙联合小檗碱早期干预对糖尿病肾小管-间质病变的预防和治疗作用。为中医未病先防既病防变提供理论依据。

中文关键词： 2型糖尿病；糖尿病肾病；肾小管间质病变；雷公藤多甙；小檗碱

英文摘要： The onset of the tubulointerstitial lesions is characterized by the infiltration of inflammatory cell, disorder of cytokine expression and deposition of extracellular matrix.Infiltration of inflammatory cell and epithelial mesenchymal transdifferentiation of renal tubular play a key role. High glucose can increase the expression of TLR4 in renal tubules, which can activate the NF-KB. TLR4/NF- κ B pathway may play an important role in in renal tubulointerstitial lesions. Previous studies have shown that tripterygium wilfordii polyglycoside(TWP) can inhibit the production of pro-inflammatory cytokine, reduce the local inflammation of kidney, combination of TWP and berberine can both improve glomerular sclerosis and reduce tubulointerstitial lesions. Our group propose a hypothesis that the combination of TWP and berberine (the effective insulinotropic alkaloid) may prevent or delay tubulointerstitial lesions by inhibiting the TLR4/NF-κB inflammatory signaling pathway. To test this hypothesis, we plan to investigate the effects of TWP and berberine on TLR4/NF-κB inflammatory pathways and Smads signaling pathway in both type 2 diabetes rat model and tubular epithelial cells, with light microscopy,immunoelectronmicroscope, immunohistochemistry, real time PCR and western blot. This work may provide a new therapeutic strategy for the treatment and prevention of tubulointerstitial lesions in the early stage. It may also demonstrate the theory of treat before sick in Chinese traditional medicine.

英文关键词： Type 2 diabetes mellitus;Diabetic nephropathy;Tubulointerstitial lesions;Tripterygium wilfordii polyglycoside;berberine