当归补血汤调控内质网应激治疗糖尿病肾病的机制研究

Diabetic nephropathy ( DN ) is the main reason causing end-stage renal disease, and its pathological mechanism is complex. Many studies show that it relates to microcirculation disturbance, high glucose induced biochemical metabolism, oxidative stress etc. Recent research has also found that the endoplasmic reticulum stress ( ERS ), a variety of inflammatory molecules activation is one of the important mechanisms in the pathogenesis of DN. Our previous study found that:" the classic prescription of invigorating Qi and promoting blood" - - of Astragalus and Angelica Mixture reduce DN rats blood glucose, urine albumin, inhibition of rat renal tissue factor( HPA, NF-KB, TGF etc.)expression, improving the kidney function, and the above study whether through the regulation of ERS, reduce inflammation activation state to finish is not yet clear. Therefore, we use of Astragalus and Angelica Mixture on rat model of DN intervention, through the whole animal and in vitro experiments, using molecular biology, immunology technology in-depth study, to elucidate the effect of Astragalus and Angelica Mixture on regulation of ERS, p47phox and X-box binding protein 1 intervention of monocyte chemoattractant protein, transforming growth factor expression, reversal kidney damage mechanisms of DN rats. We will provide new ideas of treatment for DN with traditional Chinese medicines.

糖尿病肾病（DN）是引发终末期肾病主要原因，病理机制复杂。众多研究表明与微循环障碍、高糖引起的生化代谢异常、氧化应激等有关，近期研究还发现内质网应激（ERS）、多种炎症分子的激活是DN发病的重要机制之一。我们既往研究发现："补气生血活血"的经方- - - - 当归补血汤有降低DN大鼠血糖、尿白蛋白，抑制大鼠肾组织乙酰肝素酶、核因子-κB、转化生长因子等蛋白的表达,改善肾功能的作用，而上述研究结果是否通过调控ERS、改善炎症活化状态来完成尚未明确。 因此，使用当归补血汤对DN大鼠模型进行干预，通过整体动物和体外实验，采用分子生物学、免疫学技术进行深入研究，拟阐明当归补血汤调控ERS，p47phox、X盒结合蛋白1(X-box binding protein 1, XBP1，干预单核细胞趋化因子蛋白表达，逆转DN大鼠肾损害的作用机制，为补气生血的临床应用提供依据，为中医药治疗DN提供新思路。

糖尿病肾病(DN)是引发终末期肾病主要原因，也是导致糖尿病最终死亡的原因。因此加强DN 的防治研究尤为必要。当归补血汤有补气生血功效，本项目通过实验研究探讨其逆转DN大鼠肾损害的作用机制，为补气生血的临床应用提供依据，为中医药治疗DN提供新思路。. 整体动物实验. 实验观察发现，当归补血汤能明显缓解DN模型动物的多饮、多食、多尿等症状，降低糖尿病大鼠血糖、血脂、尿白蛋白、BUN和Scr。.实验研究证实，当归补血汤通过调节内质网应激，改善氧化应激、慢性微炎症状态，下调GRP78、p47phox、Nrf2、NF-κB、MCP-1、XBP1S等蛋白表达，达到防治DN，保护肾功能的作用。. 体外实验. 通过体外培养细胞研究表明，高糖条件下肾小球系膜细胞增殖能力明显增强，而当归补血汤含药血清对高糖条件下系膜细胞（GMC）有一定的抑制作用，而且呈一定的量效关系（P<0.05），该抑制作用与下调HYP、 Nrf2、α-SMA、MDA的表达和上调T-SOD活性有关。. 项目结果显示：有补气生血功效的当归补血汤可通过调节内质网应激，逆转DN肾损害，达到防治DN的目的。