Dongying People's Hospital, Dongying City, Shandong Province, China.
Dongying People's Hospital, Dongying City, Shandong Province, China.
Int Immunopharmacol. 2020 Jul;84:106467. doi: 10.1016/j.intimp.2020.106467. Epub 2020 Apr 25.
Diabetic nephropathy (DN), a common microvascular complication of type 2 diabetes mellitus (T2DM), causes increasing mortality and morbidity due to its high prevalence and severe consequences. Hence, it is urgent to search for effective agents that provide new insights into novel molecular therapeutic targets for DN. This study was designed to investigate the critical role of Akebia saponin D (ASD) in kidney damage, inflammation and apoptosis of renal tubular cells in DN. To probe the protective effects of ASD on DN in vivo, diabetes mellitus model was established by intraperitoneal (ip) injection of STZ (60 mg/kg) for 5 days consecutively. Besides, HG-induced human renal tubular cells (HK-2) were used to analyze the defined effects and underlying mechanism of ASD on DN in vitro. Blood glucose, insulin, serum creatinine (Scr), blood urea nitrogen (BUN), renal injury, inflammation, oxidative stress and apoptosis of renal tubular cells were respectively measured and evaluated. ASD prevented kidney damage, improved renal function and inflammatory reaction, ameliorated oxidative stress and inhibited apoptosis of renal tubular cells in DN mice via activation of NRF2/HO-1 pathway and inhibition of NF-KB pathway.
糖尿病肾病(DN)是 2 型糖尿病(T2DM)的一种常见微血管并发症,由于其高患病率和严重后果,导致死亡率和发病率不断上升。因此,迫切需要寻找有效的药物,为 DN 的新型分子治疗靶点提供新的见解。本研究旨在探讨三叶木通皂苷 D(ASD)在 DN 中肾脏损伤、肾小管细胞炎症和细胞凋亡中的关键作用。为了探究 ASD 对糖尿病肾病的保护作用,通过腹腔内(ip)注射 STZ(60mg/kg)连续 5 天建立糖尿病模型。此外,还使用高糖(HG)诱导的人肾小管细胞(HK-2)在体外分析 ASD 对 DN 的明确作用及其潜在机制。分别测量和评估了血糖、胰岛素、血清肌酐(Scr)、血尿素氮(BUN)、肾脏损伤、炎症、氧化应激和肾小管细胞凋亡。ASD 通过激活 NRF2/HO-1 通路和抑制 NF-KB 通路,防止糖尿病肾病小鼠的肾脏损伤,改善肾功能和炎症反应,减轻氧化应激,抑制肾小管细胞凋亡。