基于APN/AMPK/PPARγ正反馈环路探讨太白楤木皂苷调控线粒体稳态抑制足细胞损伤的分子机制

足细胞线粒体稳态失衡是糖尿病肾病（DN）的始动环节，APN/AMPK/PPARγ正反馈环路可从多环节调控线粒体稳态，在修复足细胞损伤中发挥关键性作用。太白楤木是秦巴山区特色药材，在我国治疗消渴症和肾虚水肿历史悠久，但其具体作用机制不清。我们前期研究发现，太白楤木皂苷（sAT）能升高体内脂联素（APN）水平、改善糖脂代谢异常和线粒体功能障碍，降低血肌酐和尿素氮水平，减轻肾间质纤维化程度，提示其可能具有肾保护作用。预实验证实，sAT可减轻足细胞线粒体损伤，激活足细胞AMPK和PPARγ。为进一步证实APN/AMPK/PPARγ正反馈环路在sAT调节线粒体稳态中的作用，本课题拟从整体动物、细胞和分子等多层面，采用ELISA、Western blot和siRNA干扰等技术对其进行深入探讨。完成本课题不仅为sAT临床应用提供理论依据，也为DN防治药物的开发提供新思路，具有重要的理论和临床价值。

Mitochondrial homeostasis disorder of podocyte is the primary reason for diabetic kidney (DN). APN/AMPK/PPARγ has regulation effects on mitochondrial homeostasis through several aspects, and plays a key role in repairing podocyte injury. Aralia taibaiensis, a competitive medicinal herb from Qinba mountainous region, has a long history in the treatment of diabetes and kidney deficiency. However, its mechanism is largely unknown to us. Our previous study demonstrated that the total saponin extract from Aralia taibaiensis(sAT) increased adiponectin (APN) levels, reduced the fasting blood glucose, serum creatinine and urea nitrogen, improved renal interstitial fibrosis showing protective effects against renal injury in diabetic rats. The preliminary experiment suggested that sAT reduced mitochondrial dysfunction, activated AMPK and PPARγ in podocyte. To further elucidate the important role of the APN/AMPK/PPARγ positive feedback loop in the protection of podocytes by sAT, ELISA, Western blot, siRNA interference and other related technology were used on the animal, cellular and molecular levels. These studies not only provide a new experimental basis for prevention and treatment of DN, but also provides new research strategies in preventing and treating DN in clinical.