Evaluation of the Effects of High Uric Acid on Glucolipid Metabolism, Renal Injury and the Gut Microbiota in Diabetic Male Hamsters with Dyslipidemia.

IF 4.1 3区 环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES
Toxics Pub Date : 2025-09-04 DOI:10.3390/toxics13090751
Liang He, Miao Miao, Qingxiangzi Li, Jufen Cheng, Rui Li
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Abstract

The prevalence of hyperuricemia with elevated serum uric acid is increasing worldwide. However, the effects of high uric acid on diabetic patients with dyslipidemia and the mechanisms underlying these effects remain unexplored. This study aimed to develop a novel diabetic model of hyperuricemia and dyslipidemia in male hamsters to evaluate the effects of high uric acid on glucolipid metabolism, renal injury and the gut microbiota. Twelve healthy hamsters were randomly divided into two groups and fed with a normal diet and high-fat/cholesterol diet (HFCD), respectively. Twenty-four diabetic hamsters were randomly divided into four groups receiving a normal diet; HFCD; potassium oxonate (PO) treatment (intragastric PO at doses of 350 mg/kg and adenine at doses of 150 mg/kg with 5% fructose water); and PO treatment with HFCD, respectively. After 4 weeks, all animals were dissected for determining serum biochemical indicators, tissue antioxidant parameters, renal pathological changes, target gene expressions, fecal short-chain fatty acids content, and the gut microbiota composition. The results showed that a hamster model with hyperuricemia and dyslipidemia was successively established by the combination of PO treatment and HFCD, in which serum uric acid, glucose, triglyceride and total cholesterol levels reached 499.5 ± 61.96 μmol/L, 16.88 ± 2.81 mmol/L, 119.88 ± 27.14 mmol/L and 72.92 ± 16.62 mmol/L, respectively. PO treatment and HFCD had synergistic effects on increasing uric acid, urea nitrogen, creatinine levels, liver xanthine oxidase activity, plasminogen activator inhibitor-1 and transforming growth factor-β expressions, and the relative abundance of Lleibacterium (p < 0.05); in addition, they caused glomerular mesangial cells and matrix proliferation, protein casts and urate deposition. High uric acid was closely related to decreased antioxidant capacity; decreased renal vascular endothelial growth factor expression; increased acetic acid content; decreased butyric, propanoic, and isobutyric acid levels; decreased Firmicutes to Bacteroidetes ratios (p < 0.05); and altered epithelial integrity and structure of the gut microbiota in diabetic hamsters. The findings indicate that high uric acid affects the glucolipid metabolism, accelerates renal damage, and disrupts the balance of intestinal flora in diabetic animals, which provides a scientific basis for metabolic syndrome prevention and control in diabetes.

高尿酸对糖尿病伴血脂异常雄性仓鼠糖脂代谢、肾损伤及肠道菌群影响的评价
高尿酸血症伴血清尿酸升高的患病率在世界范围内呈上升趋势。然而,高尿酸对糖尿病合并血脂异常患者的影响及其机制尚不清楚。本研究旨在建立一种新型的雄性仓鼠糖尿病高尿酸血症和血脂异常模型,以评估高尿酸对糖脂代谢、肾损伤和肠道微生物群的影响。选取健康仓鼠12只,随机分为两组,分别饲喂正常饲粮和高脂/胆固醇饲粮。24只糖尿病仓鼠随机分为四组,给予正常饮食;HFCD;氧酸钾(PO)处理(PO灌胃剂量350 mg/kg,腺嘌呤剂量150 mg/kg,加5%果糖水);和PO分别用HFCD处理。4周后解剖各组动物,测定血清生化指标、组织抗氧化参数、肾脏病理变化、靶基因表达、粪便短链脂肪酸含量、肠道菌群组成。结果表明,PO联合HFCD建立了高尿酸血症和血脂异常的仓鼠模型,血清尿酸、葡萄糖、甘油三酯和总胆固醇水平分别达到499.5±61.96 μmol/L、16.88±2.81 mmol/L、119.88±27.14 mmol/L和72.92±16.62 mmol/L。PO处理和HFCD处理在提高尿酸、尿素氮、肌酐水平、肝黄嘌呤氧化酶活性、纤溶酶原激活物抑制剂-1和转化生长因子-β表达及Lleibacterium相对丰度方面具有协同作用(p < 0.05);此外,它们还引起肾小球系膜细胞和基质增生、蛋白铸型和尿酸沉积。高尿酸与抗氧化能力下降密切相关;肾血管内皮生长因子表达降低;醋酸含量增加;丁酸、丙酸和异丁酸水平降低;厚壁菌门与拟杆菌门之比降低(p < 0.05);改变了糖尿病仓鼠的上皮完整性和肠道微生物群的结构。研究结果提示,高尿酸影响糖尿病动物糖脂代谢,加速肾脏损害,破坏肠道菌群平衡,为糖尿病代谢综合征的防治提供科学依据。
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来源期刊
Toxics
Toxics Chemical Engineering-Chemical Health and Safety
CiteScore
4.50
自引率
10.90%
发文量
681
审稿时长
6 weeks
期刊介绍: Toxics (ISSN 2305-6304) is an international, peer-reviewed, open access journal which provides an advanced forum for studies related to all aspects of toxic chemicals and materials. It publishes reviews, regular research papers, and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in detail. There is, therefore, no restriction on the maximum length of the papers, although authors should write their papers in a clear and concise way. The full experimental details must be provided so that the results can be reproduced. Electronic files or software regarding the full details of calculations and experimental procedure can be deposited as supplementary material, if it is not possible to publish them along with the text.
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