Abstract

This study was to investigate the role of total flavonoids of hawthorn leaves (TFHL) in oxidative stress injury in rats with diabetic nephropathy (DN). CCK-8 method was used to study the effect of TFHL on the oxidative damage of kidney HK-2 cells induced by H2O2. 40 Sprague-Dawley (SD) rats with DN induced by streptozotocin were divided into normal saline group and treatment groups treated with TFHL (10, 20, 40 mg/kg). During the 6 weeks of treatment, metabolic parameters such as body weight and fasting blood glucose levels were recorded along with analysis of renal function, levels of renal tissue apoptosis, and fibrosis-related factors. The relative levels of Nrf-2/ARE pathway-related factors in kidney tissue were detected by qPCR and Western blot. 320 μg/mL TFHL significantly improved the survival rate of HK-2 cells with oxidative damage (92.9%). In treatment group, GPX1, SOD2 and GSH were significantly up-regulated, leading to down-regulation of ROS. In addition, after administration for 6 weeks, TFHL improved the renal function of DN rats and worsened the morphology of nephropathy. They also improved Bcl-2, Nrf-2, NQO-1 and HO-1 levels, and regulated Nrf-2/ARE signaling, thus having a protective effect on the kidney tissue of DN rats. After TFHL acted on kidney cells, the nuclear expression of Nrf-2 protein was significantly increased. TFHL pretreatment up-regulated NQO-1, Nrf-2 and HO-1. Our data showed that in DN rats, TFHL protected renal cells and alleviated renal tissue damage.

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