微量白蛋白尿作为糖尿病肾病（DN）早期诊断依据欠敏感，DN需更早诊断。课题组通过动物及临床研究提出“IGT肾病”概念，证实“IGT肾病”以肾小管结构损伤和功能障碍为特征，但机制不清。提出代偿性高胰岛素血症通过影响肾小管周毛细血管内皮细胞舒缩功能，致毛细血管舒缩失衡，肾小管缺血损伤，出现肾小管性蛋白尿和尿外泌体miRNAs表达异常假说。IGT属中医“脾瘅”范畴，泻心汤对DN有较好疗效。课题以OLETF大鼠为对象，观察IGT/DM各阶段肾小管周毛细血管内皮细胞功能和微循环变化及肾小管损伤，以内皮细胞和肾小管上皮细胞为对象，观察高胰岛素通过相关通路对内皮细胞舒缩和肾小管重吸收影响，揭示肾小管微循环障碍在IGT肾病发病中的作用，探讨尿外泌体miRNAs对IGT肾病的诊断价值；同时应用组分配伍方法观察泻心汤主药有效组分大黄素和黄连素对IGT肾病的防治作用。推进DN更早期诊治，丰富中医“治未病”理论。

Microalbuminuria is not so sensitive for detecting earlier diabetic nephropathy, and earlier detecting for diabetic nephropathy is in pressing need. Based on our previous work, we come up with a concept of “IGT nephropathy” innovatively which is characterized by renal tubular structural damage and functional disturbance, but the mechanism is still not clear. So we hypothesize that compensatory hyperinsulinemia will lead to contractile and relaxant disfunction of peritubular microvessels, renal tubular ischemic injury, and ultimately resulting in tubular proteinuria and abnormal expression of urinary exosome miRNAs. In Traditional Chinese Medicine, IGT belongs to “Pi-dan”, and xie-xin decoction shows a better curative effect. So we intend to observe changes of endothelial cell function of peritubular vessels, microcirculation and renal tubular injury in different stages of IGT/DM development dynamically in OLETF rats. We also intend to observe the impact of hyperinsulinemia on endothelial cell contractile and relaxant function and epithelial cell function through related pathways in vitro respectively to uncover the possible mechanism of renal microcirculation disturbance in “IGT nephropathy”, and discuss the diagnostic value of urinary exosome miRNAs for “IGT nephropathy”. In addition, we also observe the preventive and therapeutic effects of the two main components of xie-xin decoction, emodin and berberin, on “IGT nephropathy”. Our results will push on earlier detection and treatment of diabetic nephropathy, and enrich the “preventive treatment of disease” theory of Traditional Chinese Medicine.