Study on the Influence and Mechanism of Resveratrol on Cognitive Impairment in Chronic Kidney Disease Rats Through Regulating Gut Microbiota and the TLR4/NFκB Pathway

作者：Binbin Shao, Yanfei Nong, Yongshuang Lin, Yan Meng, Yi Zhou, Meiying Huang, Feifan Huang, Jie Wang · 发表于：Journal of Inflammation Research · 年份：2025 · DOI：10.2147/jir.s510867 · 被引用次数：10 · 研究领域：Gut microbiota and health、Neuroinflammation and Neurodegeneration Mechanisms、Tryptophan and brain disorders

Objective: To investigate the mechanism by which resveratrol (Res) ameliorates cognitive impairment (CI) in chronic kidney disease (CKD) rats through modulation of gut microbiota and suppression of inflammation. Methods: A CKD model was established in rats via two intravenous injections of doxorubicin (4 mg/kg, 2 weeks apart). After 8 weeks, renal function and histopathological assessments were performed to confirm the establishment of the CKD model.Rats were divided into control, CKD, and CKD+Res groups. The CKD+Res group received intragastric Res for 6 weeks. Cognitive function was assessed using the Morris water maze. Serum Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Lipopolysaccharide (LPS) levels were measured via ELISA. Histopathology evaluated kidney, colon, and hippocampal damage. Gut microbiota composition was analyzed by 16S rRNA sequencing, and hippocampal Toll-Like Receptor 4 (TLR4)/ the Nuclear Factor-κB (NFκB) pathway proteins were quantified via Western blot. Results: CKD groups exhibited elevated 24-hour urinary albumin, serum urea nitrogen, and creatinine ( P < 0.01), with glomerular atrophy. During water maze navigation (days 3– 4), CKD groups showed prolonged escape latency and increased swimming distance versus controls ( P < 0.05), which Res intervention alleviated ( P < 0.05). In the spatial probe test, CKD rats had fewer platform crossings and shorter target quadrant occupancy ( P < 0.01; P < 0.05), both improved by Res ( P < 0.05). H...