Dehydrozingerone ameliorate renal structures compromised in diabetic nephropathy

Kidney structural integrity is critical for bodily excretory mechanism. Diabetes has been considered as one of the major risk factors for chronic kidney disease, but the underlying mechanism remains elusive. The present study investigates the transcriptomic and proteomic profiling of long-term impact of high-fat diet on renal tissue in mice and role of dehydrozingerone (DH) in reinstating the normal kidney function. Animals were divided into four groups- healthy (NCD+Veh), diabetic (HFD-STZ), healthy+DH (NCD+Veh+DH) and treatment (HFD-STZ+DH). 65th days of HFD-fed C57BL/6 mice developed diabetes and kidney dysfunction evident by albuminuria, proteinuria, and glucotoxicity with accumulation of glucose, triglyceride, cholesterol, and total protein in blood serum. The HFD-fed kidney showed renal injuries, including prominent defects in the glomerular filtration system by downregulation of proteins involved in transport, metabolic process, energy production, anti-oxidation, etc. Downregulation of lipid metabolism is most impacted metabolic process under diabetic condition. Downregulation of transport proteins mainly impact the functioning of podocytes, cell adhesion and cytoskeletal rearrangement. HFD feeding also increased oxidative stress and induced mitochondrial dysfunction, and thereby activating the pro-apoptotic pathway. Both transcriptomic and proteomic studies revealed the potential of Dehydrozingerone in attenuating the diabetic condition by positively regulating transport system, mitochondrial function, lipid metabolism, DNA damage and epigenetic alteration, and oxidative stress, which reinstate the kidney function.肾脏结构完整性对机体排泄功能至关重要。糖尿病已被认定为慢性肾脏病的主要危险因素之一，但其潜在发病机制仍未明确。本研究针对高脂饮食对小鼠肾脏组织的长期影响开展转录组学与蛋白质组学分析，并考察脱氢姜酮（dehydrozingerone, DH）对肾脏正常功能的恢复作用。实验动物分为四组：正常对照组（NCD+Veh）、糖尿病模型组（HFD-STZ）、正常对照+DH干预组（NCD+Veh+DH）以及治疗组（HFD-STZ+DH）。高脂饮食喂养65天后，C57BL/6小鼠出现糖尿病及肾功能异常，表现为白蛋白尿、蛋白尿与糖毒性，同时血清中葡萄糖、甘油三酯、胆固醇及总蛋白水平显著升高。高脂饮食喂养组小鼠的肾脏可见损伤，包括肾小球滤过系统的显著异常，该异常与转运、代谢、能量产生、抗氧化等相关蛋白的下调密切相关。糖尿病状态下，脂质代谢下调是受影响最为显著的代谢过程。转运蛋白的下调主要影响足细胞功能、细胞黏附及细胞骨架重排。高脂饮食喂养还可加剧氧化应激、诱发线粒体功能障碍，进而激活促凋亡通路。转录组学与蛋白质组学分析均证实，脱氢姜酮可通过正向调控转运系统、线粒体功能、脂质代谢、DNA损伤与表观遗传修饰以及氧化应激，从而改善糖尿病状态，恢复肾脏正常功能。