通过检测高尿酸血症大鼠血清代谢谱的变化, 探讨代谢组学在高尿酸血症研究中的应用。将20 只清洁级健康SD(Sprague-Dawley)大鼠随机分为高尿酸血症模型组(10 只)和空白对照组(10 只), 每日采用酵母膏(YEP)21 g·kg-1·d-1给予喂养, 氧氢酸钾(OA)以200 mg-1·kg-1·d-1腹腔注射1 次, 建立高尿酸血症大鼠模型。第28 日收集空白对照组和模型组大鼠血清, 进行1H-NMR 谱测定和主成分分析。与空白对照组大鼠相比, 模型组大鼠血清中糖蛋白、丙酮酸、丙氨酸、异亮氨酸、亮氨酸显著增加, 而甲酸浓度及极低密度脂蛋白、不饱和脂肪酸、丙酮显著降低。由此得出, 高尿酸血症大鼠血清代谢组学发生明显变化, 血浆代谢组学在一定程度上反映高尿酸血症大鼠的病理生理变化。
The serum metabonomic variation in hyperuricemia rats was investigated in order to explore the application of metabonomics in research of hyperuricemia. The animals were divided into two groups at random, i.e., the normal group (n=10) and the model group (n=10). The rat model was treated with yeast extract powder(YEP)as 21 g·kg-1·d-1 and OA paired 20 g/L mother liquor with sterile distilled water. The two group's serum was collected and its 1H nuclear mannetic resonance (1H-NMR) spectra was acquired. Compared with the normal control group, the model group′s glycoprotein, pyruvic acid, alanine, isoleucine, leucine were all increased, however, formaldehyde, VLDL, unsaturated fatty acid, and acetone were reduced. Significant changes in serum metabonomics found in the hyperuricemia rat models might reflect to a certain extent the pathological changes of hyperuricemia rat models.
[1] Erkmen U M, Sezer S, Bal Z, et al. Post-transplant Hyperuricemıa as a cardıovascular risk factor[J]. Transplantation Proceedings, 2015, 47(4): 1146-1151.
[2] Thomas M, Ian F, George N, et al. Protocol of the Febuxostat versus Allopurinol Streamlined Trial (FAST): A large prospective, randomised, open, blinded endpoint study comparing the cardiovascular safety of allopurinol and febuxostat in the management of symptomatic hyperuricaemia[J]. British Medical Journal of Open, 2014, 4(7): e005354.
[3] Ciarla S, Struglia M, Giorgini P, et al. Serum uric acid levels and metabolic syndrome[J]. Archives of Physiology and Biochemistry, 2014, 120(3): 119-122.
[4] Odden M C, Amadu A R, Smit E, et al. Peralta CA uric acid levels, kidney function, and cardiovascular mortality in US adults: National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2002[J]. American Journal of Kidney Diseases, 2014, 64(4): 550-557.
[5] Hanna M H, Brophy P D. Metabolomics in pediatric nephrology: Emerging concepts[J]. Pediatric Nephrology, 2014, 30(6): 881-887.
[6] Mussap M, Noto A, Fanos V, et al.Emerging biomarkers and metabolomics for assessing toxic nephropathy and acute kidney injury (AKI) in neonatology[J]. BioMed Research International, 2014, 60(25): 26-41.
[7] Jayavelu N D, Bar N S. Metabolomic studies of human gastric cancer: Review[J]. World Journal of Gastroenterol, 2014, 20(25): 8092-8101.
[8] Yuan G, Al shali K Z, Hegele R A, et al. Hypertriglyceridemia: Itsetiology, effects and treatment, hypertriglyceridemia: Its etiology, effects and treatment[J]. Canadian Medical Association journal, 2007, 176(8):1113-1120.
[9] 迪丽达尔·希力甫, 赵平, 张向阳, 等. 酵母膏联合氧嗪酸钾构建高尿酸血症模型大鼠继发的心血管病变[J]. 中国工程与临床康复, 2012, 16(11): 1994-1998. Dilidaer Sherip, Zhao Ping, Zhang Xiangyang, et al. Development of secondary cardiovascular diseaseinhyperuricemia modelrats induced by yeast extract combined with oteracil potassium[J]. Chinese Journal of Tissue Engineering Research, 2012, 16(11): 1994-1998.
[10] Jin Y L, Zhu T, Xu L, et al. Uric acid levels, even in the normal range, are associated with increased cardiovascular risk: The Guangzhou biobank cohort study[J]. International Journal of Cardiology, 2013, 168 (3): 2238-2241.
[11] Bain J R. Targeted metabolomics finds its mark in diabetes research[J]. Diabetes, 2013, 62(2): 349-351.
[12] Hu M, Tomlinson B. Current perspectives on rosuvastatin[J]. Journal of Integrated Blood Pressure Control, 2013, 18(6): 15-25.
[13] 徐秋莲, 杜简秋, 刘淑杰, 等. 阿托伐他汀钙对慢性充血性心力衰竭患者血浆内皮素及血清尿酸水平的影响[J]. 中国老年医学杂志, 2005, 7(25): 845-846. Xu Qiulian, Du Jianqiu, Liu Shujie, et al. Effect of atorvastatin calcium on the levels of plasma endothelin and serum uric acid in patients with chronic heart failure[J]. Chinese Journal of geriatric medicine, 2005, 7(25): 845-846.
[14] Strippoli G F, Navaneethan S D, Johnson D W, et al. Effects of statins in patients with chronic kidney disease: Meta-analysis and metaregression of randomized controlled trials[J]. British Medical Journal, 2008, 236(7645): 645-651.