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Abstract: TH-PO900

QiDiTangShen Granules Activated Renal Autophagy by Regulating Nutrient-Sensing Signal Pathways in db/db Mice

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Wang, Xiangming, Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine, Peking, Peking, China
  • Zhao, Li, Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine, Peking, Peking, China
  • Ajay, Amrendra Kumar, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
Background

Proteinuria is an independent risk factor for diabetic nephropathy (DN). QiDiTangShen granules(QDTS) have been proven to reduce the proteinuria in patients with DN effectively. The present study was aimed at investigating the renoprotective mechanism of QDTS granules.

Methods

Firstly, main components of QDTS were identified by ultra-high liquid chromatography-tandem mass spectrometry and pharmacological databases, among which active components were screened by oral bioavailability and drug-likeness.The role on autophagy-related nutrient-sensing signal molecules was retrieved and analyzed through the Pubmed database. Secondly, C57BL/6J mice as normal control, db/db mice were randomly divided into three groups (model control,Valsartan and QDTS), and given intragastric administration for 12 weeks. Effectiveness and safety indicators, such as fasting and random blood glucose, urinary albumin excretion (UAE) and injury markers of liver and kidney were tested by glucose oxidase and radioimmunoassay, enzyme-linked immunosorbent assay and biochemical methods, respectively. Renal histological changes were evaluated by H&E, methenamine silver and Masson's trichrome staining.The quality and quantity of mitochondria and autophagic vesicles was observed by transmission electron microscope. Expressions of proteins related to nutrient-sensing signals and autophagy were assessed by western blot and immunofluorescence.

Results

13 active components were screened from 78 components identified. Over half the components had already been reported to improve nutrient–sensing signals (AMPK, SIRT1 and mTOR). Compared with the model group, QDTS reduced UAE independent of blood glucose control, ameliorated renal mesangial hyperplasia and deposition of collagen fiber, improved the quality of mitochondria and the quantity of autophagic vesicles of renal tubular cells in db/db mice.The expression of Atg14,Beclin1and LC3-II were up-regulated, autophagic substrate transporter p62 was down-regulated in QDTS group. The expression of SIRT1, the proportion of both p-AMPK (thr172) / AMPK (total) and p-mTOR (ser2448) / mTOR (total) were also regulated by QDTS.

Conclusion

QDTS granules may regulate the nutrient-sensing signaling pathways to improve the renal autophagic activity and exert renoprotective effect.

Funding

  • Government Support - Non-U.S.