Effect of Prolonged Fasting on Uric Acid Metabolism and Its Regulation Mechanism
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摘要: 为研究长期禁食过程中大鼠尿酸代谢的变化及其潜在的调控机制，以Sprague-Dawley（SD）大鼠为动物模型，通过病理组织切片、生化检测、荧光定量PCR（qRT-PCR）以及蛋白免疫印迹（Western blotting）等方法分析不同禁食时间（1，2，3，5，7天）大鼠尿酸水平及其代谢相关基因和蛋白的表达变化。结果表明，长期禁食未对大鼠肾脏组织产生明显的损伤，引起了血尿酸水平上升、尿尿酸水平波动性变化和血液尿酸酶活性升高；随着禁食时间的延长，主要尿酸转运蛋白的mRNA和蛋白表达水平逐渐上调。长期禁食过程中大鼠尿酸代谢变化可能与尿酸转运蛋白及尿酸酶活性有关。Abstract: To investigate the changes of uric acid metabolism in rats during prolonged fasting and its potential regulatory mechanism. Sprague-Dawley (SD) rats were used as animal models. The changes of uric acid level and metabolism-related gene and protein expression in rats during different fasting periods (1, 2, 3, 5, and 7 days) were analyzed by pathological tissue sections, biochemical tests, quantitative PCR (qRT-PCR), and western blotting. The results showed that prolonged fasting did not cause significant damage to kidney tissue, but remarkedly increased the blood uric acid level and blood uricase activity. It also resulted in fluctuating changes in urine uric acid level. The mRNA and protein expression levels of main uric acid transporters were increased gradually with the fasting duration. The elevation of serum uric acid caused by prolonged fasting is related to uric acid transporter and uricase activity.
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Key words:
- Prolonged fasting /
- Uric acid metabolism /
- Regulatory mechanism /
- Hypometabolism
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图 1 不同禁食时间各组大鼠肾病理形态学变化（n=3）。（a）正常对照组肾脏，（b）禁食1天肾脏，（c）禁食2天肾脏，（d）禁食3天肾脏，（e）禁食5天肾脏，（f）禁食7天肾脏。红色箭头表示肾小球，蓝色箭头表示肾小管上皮细胞，黑色箭头表示上皮细胞脱落及炎症细胞浸润
Figure 1. Pathological changes of the kidneys during different fasting duration in rats (n=3 in each group). (a) Normal control group, (b) fasting for 1 day, (c) fasting for 2 days, (d) fasting for 3 days, (e) fasting for 5 days, (f) fasting for 7 days. Red arrow: glomerulus. Blue arrow: tubular epithelial cells. Black arrow: epithelial cell exfoliation and inflammatory cell infiltration
图 2 不同禁食时间各组大鼠肾脏组织病理形态学变化检测评分（n=3）
Figure 2. Histological scores in kidneys during different fasting duration in rats (n=3 in each group)
图 3 不同禁食时间大鼠血肌酐（a）和尿素（b）变化。n=6，**P<0.01，与 0 d（对照组）比较
Figure 3. Changes of blood creatinine (a) and urea (b) during different fasting duration in rats. n=6, **P<0.01, compared with 0 d (control group)
图 4 不同禁食时间大鼠血尿酸（a）和尿尿酸（b）变化。n=6，*P<0.05，**P<0.01，与 0 d（对照组）比较
Figure 4. Changes of blood uric acid (a) and urine uric acid (b) during different fasting duration in rats. n=6, *P<0.05, **P<0.01, compared with 0 d (control group)
图 5 不同禁食时间大鼠血液尿酸酶（a）和尿液尿囊素（b）水平变化。n=6，*P<0.05，**P<0.01，与 0 d（对照组）比较
Figure 5. Changes of blood uricase (a) and urine allantoin (b) during different fasting duration in rats. n=6, *P<0.05, **P<0.01, compared with 0 d (control group)
图 6 不同禁食时间大鼠尿酸转运蛋白mRNA表达水平变化。n=6，*P<0.05，**P<0.01，与 0 d（对照组）比较。（a） GLUT9，（b） URAT1，（c） OAT1，（d） Mrp4，（e） UAT，（f） NPT1
Figure 6. mRNA changes of urate transporter during different fasting duration in rats. n=6, *P<0.05, **P<0.01, compared with 0 d (control group). (a) GLUT9, (b) URAT1, (c) OAT1, (d) Mrp4, (e) UAT, (f) NPT1
图 7 不同禁食时间大鼠主要尿酸转运蛋白（GLUT9，URAT1，UAT）的蛋白表达水平变化。n=6，*P<0.05，**P<0.01，与 0 d（对照组）比较。（a）GLUT9蛋白相对表达量，（b）URAT1蛋白相对表达量，（c）UAT蛋白相对表达量
Figure 7. Protein changes of major urate transporter (GLUT9, URAT1, UAT) during different fasting duration in rats. n=6, *P<0.05, **P<0.01, compared with 0 d (control group). (a) The protein relative expression of GLUT9 protein, (b) the protein relative expression of URAT1 protein, (c) the protein relative expression of UAT protein
图 8 不同禁食时间大鼠血尿酸与主要尿酸转运蛋白mRNA和蛋白相对表达量之间相关性分析。血尿酸与尿酸转运蛋白GLUT9 （a），URAT1（b），UAT（c） mRNA相对表达量，以及GLUT9（d），URAT1（e），UAT（f）蛋白相对表达量之间相关性分析
Figure 8. Correlation analysis between blood uric acid and mRNA and protein relative expression of main uric acid transporter during different fasting duration in rats. The correlation analysis between blood uric acid and the mRNA expression and protein expression of (a)(d) GLUT9, (b)(e) URAT1, (c)(f) UAT
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