Shao Binbin, Nong Yanfei, Lin Yongshuang, Meng Yan, Zhou Yi, Huang Meiying, Huang Feifan, Wang Jie
Graduate School, Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People's Republic of China.
The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, 530000, People's Republic of China.
J Inflamm Res. 2025 May 8;18:6049-6060. doi: 10.2147/JIR.S510867. eCollection 2025.
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.
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.
CKD groups exhibited elevated 24-hour urinary albumin, serum urea nitrogen, and creatinine ( < 0.01), with glomerular atrophy. During water maze navigation (days 3-4), CKD groups showed prolonged escape latency and increased swimming distance versus controls ( < 0.05), which Res intervention alleviated ( < 0.05). In the spatial probe test, CKD rats had fewer platform crossings and shorter target quadrant occupancy ( < 0.01; < 0.05), both improved by Res ( < 0.05). Hippocampal neuronal damage and elevated serum IL-6, TNF-α, and LPS levels ( < 0.01) were observed in CKD rats, while Res reduced IL-6 and LPS ( < 0.05). Western blot revealed upregulated TLR4/NFκB pathway activation in the CKD group ( < 0.01), suppressed by Res ( < 0.05). Gut microbiota analysis showed increased Gram-negative bacteria in CKD rats and higher Gram-positive bacteria abundance in the Res group. LPS biosynthesis was enhanced in CKD rats ( < 0.05) but attenuated by Res.
探讨白藜芦醇（Res）通过调节肠道微生物群和抑制炎症来改善慢性肾脏病（CKD）大鼠认知障碍（CI）的机制。
通过两次静脉注射阿霉素（4mg/kg，间隔2周）建立大鼠CKD模型。8周后，进行肾功能和组织病理学评估以确认CKD模型的建立。将大鼠分为对照组、CKD组和CKD+Res组。CKD+Res组接受胃内给予Res 6周。使用莫里斯水迷宫评估认知功能。通过酶联免疫吸附测定法测量血清白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和脂多糖（LPS）水平。组织病理学评估肾脏、结肠和海马损伤。通过16S rRNA测序分析肠道微生物群组成，并通过蛋白质印迹法定量海马Toll样受体4（TLR4）/核因子-κB（NFκB）通路蛋白。
CKD组24小时尿白蛋白、血清尿素氮和肌酐升高（<0.01），伴有肾小球萎缩。在水迷宫导航期间（第3-4天），CKD组与对照组相比逃避潜伏期延长且游泳距离增加（<0.05），Res干预可缓解（<0.05）。在空间探索试验中，CKD大鼠穿越平台的次数较少且在目标象限的停留时间较短（<0.01；<0.05），Res均使其得到改善（<0.05）。在CKD大鼠中观察到海马神经元损伤以及血清IL-6、TNF-α和LPS水平升高（<0.01），而Res降低了IL-6和LPS（<0.05）。蛋白质印迹显示CKD组中TLR4/NFκB通路激活上调（<0.01），Res可抑制（<0.05）。肠道微生物群分析显示CKD大鼠中革兰氏阴性菌增加，而Res组中革兰氏阳性菌丰度更高。CKD大鼠中LPS生物合成增强（<0.05），但Res可使其减弱。
