Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China (mainland).
Department of Nephrology, Jingzhou Central Hospital, Jingzhou, Hubei, China (mainland).
Med Sci Monit. 2020 Jun 27;26:e924372. doi: 10.12659/MSM.924372.
BACKGROUND Diabetic nephropathy (DN) is one of the chronic microvascular complications of diabetes. This study focused on the protective effects of pyrroloquinoline quinone (PQQ) on oxidative stress (OS) in DN. MATERIAL AND METHODS Thirty Sprague Dawley rats were randomly selected for this study; 10 rats were randomly selected as the control group. The other 20 rats were established for the DN model. After establishment of the successful model, the DN model rats were randomly divided into a DN group and a PQQ group. The PQQ group was fed with a PQQ diet. Blood urea nitrogen (BUN), serum creatinine (SCr), and blood glucose levels were measured in each group, and OS-related protein expression and AMPK pathway were detected by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). At the same time, we constructed a DN model by culturing NRK-52E cells with high glucose to detect the molecular mechanisms. RESULTS The kidney function of the DN group was significantly decreased, SCr and BUN levels were significantly increased, and the renal structure under the microscope was disordered, and interstitial edema was obvious. The expression of SOD1, SOD2, GPX1, and GPX3 were significantly decreased, and the level of reactive oxygen species (ROS) was significantly increased. PQQ treatment can effectively alleviate renal function, improve structural damage, and inhibit OS. In vivo, PQQ can effectively inhibit high glucose-induced OS damage and activate the AMPK/FOXO3a signaling pathway. CONCLUSIONS PQQ improves renal structural damage and functional damage, and protects kidney cells in DN by inhibiting OS, which may be related to activating the AMPK/FOXO3a pathway.
糖尿病肾病(DN)是糖尿病的慢性微血管并发症之一。本研究主要关注吡咯喹啉醌(PQQ)对 DN 中氧化应激(OS)的保护作用。
本研究随机选择 30 只 Sprague Dawley 大鼠;随机选择 10 只大鼠作为对照组。其余 20 只大鼠建立 DN 模型。成功建立模型后,将 DN 模型大鼠随机分为 DN 组和 PQQ 组。PQQ 组给予 PQQ 饮食。测量各组大鼠的血尿素氮(BUN)、血清肌酐(SCr)和血糖水平,采用 Western blot 和实时定量聚合酶链反应(qRT-PCR)检测 OS 相关蛋白表达和 AMPK 通路。同时,通过高糖培养 NRK-52E 细胞构建 DN 模型,检测分子机制。
DN 组大鼠肾功能明显下降,SCr 和 BUN 水平明显升高,显微镜下肾组织结构紊乱,间质水肿明显。SOD1、SOD2、GPX1 和 GPX3 的表达明显下降,活性氧(ROS)水平明显升高。PQQ 处理可有效缓解肾功能下降,改善结构损伤,抑制 OS。体内,PQQ 可有效抑制高糖诱导的 OS 损伤,激活 AMPK/FOXO3a 信号通路。
PQQ 通过抑制 OS 改善 DN 大鼠的肾结构损伤和功能损伤,保护肾细胞,这可能与激活 AMPK/FOXO3a 通路有关。