雷公藤多甙联合小檗碱早期干预对2型糖尿病肾病肾小球屏障功能的影响研究

Abnormal glomerular fiter function underlies the pathology of the early stage diabetic nephropathy (DN). Previous clinical studies have shown that tripterygium wilfordii polyglycoside(TWP) remarkably reduced proteinuria in DN. Recently, inflammation has been suggested as a risk factor in the pythogenesis of DN. Macrophage invasion in the kidney was also confirmed with the DN rat model，which can be alleviated by TWP intervention. SOCS signaling pathway has been known to inhibit inflammation through JAK and NF-κB pathways. Our group proposed a hypothesis that the combination of TWP and berberine (the effective insulinotropic alkaloid) may improve glomerular fiter barrier function by activating the SOCS signaling pathway, thus prevent the development of DN in early stage. To test this hypothesis, we planned to investigate the effects of TWP and berberine on glomerular filtration and inflammatory pathways in both type 2 diabetes rat model and glomerular cellline,with immunoelectronmicroscope, real time PCR, western blot and immunohistochemistry . This work may provide a new therapeutic strategy for the treatment and prevention of DN in the early stage. It may also demonstrate the theory of "treat before sick" in Chinese traditional medicine.

肾小球滤过屏障功能障碍是早期糖尿病肾病的病理基础。前期临床工作发现，雷公藤多甙可显著降低糖尿病肾病尿蛋白水平，动物实验表明雷公藤多甙可影响糖尿病肾病大鼠肾组织中巨噬细胞浸润。在炎症信号通路中，SOCS可负反馈抑制JAK和NF-κB信号通路，从而抑制炎症介质和细胞因子的产生，减轻炎症反应。本课题采用有效治疗糖尿病肾病的中药成分进行配伍，提出了"雷公藤多甙联合小檗碱通过促进SOCS信号通路的表达而调节肾小球滤过屏障功能，可早期防治糖尿病肾病"的假说。本研究以2型糖尿病肾病大鼠和肾小球内皮细胞、足细胞为研究对象，应用免疫电镜、实时荧光定量PCR、Western-Blot法、免疫组化法，探讨雷公藤多甙联合小檗碱早期干预对糖尿病肾病肾小球滤过屏障功能和炎症通路的影响,为中医"治未病"防治糖尿病肾病提供理论依据。

肾小球滤过屏障功能障碍是早期糖尿病肾病的病理基础。前期临床工作发现，雷公藤多苷可显著降低糖尿病肾病尿蛋白水平，动物实验表明雷公藤多苷可影响糖尿病肾病大鼠肾组织中巨噬细胞浸润。在炎症信号通路中，SOCS可负反馈抑制JAK和NF-KB信号通路，从而抑制炎症介质和细胞因子的产生，减轻炎症反应。本课题采用有效治疗糖尿病肾病的中药成分进行配伍，验证了“雷公藤多苷联合小檗碱通过促进SOCS信号通路的表达而调节肾小球滤过屏障功能，可早期防治糖尿病肾病”的假说。本研究以2型糖尿病肾病大鼠和肾小球足细胞为研究对象，应用免疫电镜、实时荧光定量PCR、Western-Blot法、免疫组化法，探讨雷公藤多苷联合小檗碱早期干预对糖尿病肾病肾小球滤过屏障功能和炎症通路的影响，为中医“治未病”防治糖尿病肾病提供理论依据。