Polyethylene Glycol 4000 Lowers Serum Uric Acid in Uricase-deficient Rats
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摘要:
目的 观察聚乙二醇4000（PEG4000）对雄性Kunming-DY大鼠（尿酸酶缺失大鼠）的降尿酸作用。 方法 选取45d雄性Kunming-DY大鼠共24只，设对照组（n = 6）和治疗组：PEG4000高（10.5 g/L）、中（5.25 g/L）、低（2.625 g/L）剂量组各6只。对照组自由饮水，治疗组自由饮用1周。实验前后需剪尾取血，收集血清以及大鼠24 h尿液和粪便，记录24 h进食和饮水量同时收集大鼠主要组织器官。测定血清样品中的尿酸、血尿素氮和血肌酐的含量和排泄物尿酸含量以及组织器官样品尿酸含量，观察对照组和治疗组各个指标的变化。 结果 （1）对照组血尿酸高于70 µg/mL，而PEG4000（10.5、5.25 g/L）能将大鼠血尿酸降低在50~60 µg/mL之间，差异有统计学意义（P < 0.05）；与对照组相比，PEG4000（10.5、5.25、2.625 g/L）粪便排泄量增加，差异有统计学意义（P < 0.05）；（2）与对照组相比，治疗组PEG4000（5.25 g/L）血尿素氮也有明显的下降，差异有统计学意义（P < 0.05）；（3）与对照组相比，PEG4000（5.25 g/L）降低组织（心、肝、脾、肺、肾、肾上腺）的尿酸含量，差异有统计学意义（P < 0.05）；PEG4000（2.625 g/L）降低组织（肝、脾、肾、肾上腺）的尿酸含量，差异有统计学意义（P < 0.05）。 结论 （1）口服PEG4000溶液具有降尿酸作用，其降低血尿酸与增加排便有关；（2）口服PEG4000溶液可以减少肾脏尿酸负担。 -
关键词:
- Kunming-DY大鼠 /
- 尿酸酶缺失 /
- 高尿酸血症 /
- 聚乙二醇4000 /
- 降尿酸作用
Abstract:Objective To explore serum uric acid （SUA） lowering effect of polyethylene glycol 4000 （PEG4000） on male Kunming-DY rats （uricase-deficient rats）. Methods A total of 24 45-day male Kunming-DY rats were selected and divided into control group （n = 6） and treatment group: high （10.5 g/L）, medium （5.25 g/L） and low （2.625 g/L） PEG4000 dose groups with 6 rats in each group. The control group drank freely and the treatment group drank freely for 1 week. Before and after the experiment, the tail was cut and blood was collected, and the serum, urine and feces of the rats were collected for 24 hours. The food and water intake for 24 hours were recorded, and the main tissues and organs of the rats were harvested. The contents of uric acid, blood urea nitrogen and creatinine in serum samples, uric acid in excreta and uric acid in tissues and organs were tested, and the changes of indexes in control group and treatment group were compared. Results The blood uric acid in the control group was higher than 70 µg/mL, while PEG4000 （10.5 and 5.25 g/L） reduced it to 50-60 g/ml, and the difference was statistically significant （P < 0.05）. Compared with the control group, the fecal excretion of PEG4000 （10.5, 5.25, 2.625 g/L） groups increased significantly （P < 0.05）. Compared with the control group, the blood urea nitrogen of PEG4000 （5.25 g/L） in the treatment group also decreased significantly, and the difference was statistically significant （P < 0.05）. Compared with the control group, PEG4000 （5.25 g/L） group decreased the uric acid content in tissues （heart, liver, spleen, lung, kidney and adrenal gland）, and the difference was statistically significant （P < 0.05）; PEG4000 （2.625 g/L） decreased the uric acid in tissues （liver, spleen, kidney and adrenal gland）, and the difference was statistically significant （P < 0.05）. Conclusion Oral PEG4000 solution can reduce uric acid, which is related to the increase of defecation. Oral PEG4000 solution can reduce the burden of uric acid in kidney. -
Key words:
- Kunming-DY rat /
- Uricase deficiency /
- Hyperuricemia /
- PEG4000 /
- Serum uric acid lowering
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图 1 PEG4000对Kunming-DY大鼠的降尿酸作用[（
$\bar x \pm s $ ），n = 6]A：1周前后大鼠血清尿酸（SUA）变化；B：1周前后大鼠尿液尿酸（UUA）浓度变化；C：1周前后大鼠粪便尿酸（StUA）含量变化；D：1周前后24h粪便尿酸总量变化。*P < 0.05。
Figure 1. PEG4000 lowered serum uric acid in Kunming-DY rats [（
$\bar x \pm s $ ），n = 6]
图 2 PEG4000对Kunming-DY大鼠的组织尿酸、血肌酐、血尿素氮的影响[（
$\bar x \pm s $ ），n = 6]A：1周后Kunming-DY大鼠脏器尿酸（UA）含量变化；B：1周前后Kunming-DY大鼠血肌酐含量（Cr）变化；C：1周前后Kunming-DY大鼠血尿素氮（BUN）变化。*P < 0.05。
Figure 2. Effects of PEG4000 on tissue uric acid，blood creatinine and blood urea nitrogen in Kunming-DY rats [（
$\bar x \pm s $ ），n = 6]表 1 实验前后多个指标的变化值[（
$ \bar x \pm s $ ），n = 6]（1）Table 1. Changes of various indexes before and after treatment [（
$ \bar x \pm s $ ），n = 6]（1）项目 24 h尿量（mL） 尿液尿酸（μg/mL） 24 h尿液尿酸（mg） W0 W1 W1-W0 W0 W1 W1-W0 W0 W1 W1-W0 对照组 29.3 ± 5.5 31.4 ± 3.7 2.2 ± 4.4 1307.8 ± 647.2 1308.6 ± 241.2 0.8 ± 656.9 37.5 ± 19.7 41.5 ± 10.3 4.0 ± 19.3 10.5 g/L 44.7 ± 7.8 34.3 ± 4.4 −10.3 ± 11.4 1034.0 ± 638.9 877.8 ± 209.0 −156.2 ± 746.4 42.3 ± 18.6 30.0 ± 7.5 −12.3 ± 19.8 5.25 g/L 35.7 ± 1.6 43.9 ± 7.4 8.13 ± 7.7 1165.0 ± 396.5 936.3 ± 238 −228.7 ± 375.2 41.0 ± 14.4 41.1 ± 13.6 0.1 ± 17.1 2.625 g/L 37.7 ± 3.2 39.1 ± 11.1 1.4 ± 10.5 1849.2 ± 324.0 636.0 ± 288.8 −1213.2+586.1 70.3 ± 16.5 24.9 ± 11.3 −45.4 ± 25.6 F 4.65 4.31 6.20 P 0.00* 0.00* 0.00* 与对照组比较，*P < 0.05。 
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表 1 实验前后多个指标的变化值[（
$ \bar x \pm s $ ），n = 6]（2）Table 1. Changes of various indexes before and after treatment [（
$ \bar x \pm s $ ），n = 6]（2）项目 24 h粪便（g） 粪便尿酸（μg/g） 24 h粪便尿酸（mg） W0 W1 W1-W0 W0 W1 W1-W0 W0 W1 W1-W0 对照组 8.1 ± 0.9 9.6 ± 1.7 1.5 ± 1.7 137.9 ± 73.6 171.5 ± 53.8 33.6 ± 92.5 1.2 ± 0.8 1.6 ± 0.4 0.4 ± 0.9 10.5 g/L 10.1 ± 2.8 15.5 ± 2.1 5.3 ± 2.4 192.7 ± 75.5 323.6 ± 114.4 130.9 ± 102.9 2.1 ± 1.5 5.0 ± 1.9 2.9 ± 1.7 5.25 g/L 8.4 ± 1.1 14.3 ± 2.7 5.9 ± 2.8 125.5 ± 39.9 150.3 ± 40.7 24.7 ± 42.5 1.0 ± 0.3 2.1 ± 0.7 1.1 ± 0.5 2.625 g/L 9.6 ± 0.9 7.0 ± 1.0 2.6 ± 1.2 171.8 ± 41.3 107.2 ± 31.8 −64.6 ± 63.6 1.2 ± 0.3 1.0 ± 0.4 −0.2 ± 0.6 F 8.07 5.32 6.85 P 0.00* 0.00* 0.00* 与对照组比较，*P < 0.05。
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表 1 实验前后多个指标的变化值[（
$ \bar x \pm s $ ），n = 6] （3）Table 1. Changes of various indexes before and after treatment [（
$ \bar x \pm s $ ），n = 6] （3）项目 24 h排尿酸总量（mg） 24 h进食量（g） 24 h饮水量（mL） W0 W1 W1-W0 W0 W1 W1-W0 W0 W1 W1-W0 对照组 38.7 ± 19.9 43.0 ± 10.1 4.4 ± 19.0 18.1 ± 3.6 21.8 ± 1.2 3.7 ± 2.9 51.3 ± 5.5 59.4 ± 5.4 8.2 ± 7.4 10.5g/L 44.4 ± 17.7 35.0 ± 7.4 9.4 ± 20.0 20.4 ± 2.6 24.5 ± 2.4 4.1 ± 1.6 69.9 ± 12.4 72.9 ± 14.0 3.0 ± 11.6 5.25g/L 42.2 ± 19.1 41.4 ± 18.4 −0.8 ± 15.2 22.0 ± 2.8 26.9 ± 1.9 4.9 ± 3.2 56.9 ± 3.9 71.2 ± 12.7 14.3 ± 14.9 2.625g/L 57.8 ± 22.7 60.7 ± 17.7 2.9 ± 15.2 19.9 ± 0.7 23.2 ± 3.5 3.3 ± 0.7 59.6 ± 3.5 70.1 ± 7.1 13.2 ± 6.7 F 0.57 1.70 4.99 P 0.72 1.61 0.00* 与对照组比较，*P < 0.05。
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表 2 实验前后多种指标用体重校正后[（
$ \bar x \pm s $ ），n = 6] （1）Table 2. Various indexes were balanced by weight before and after treatment [（
$ \bar x \pm s $ ），n = 6] （1）项目 相对排尿量（mL/200 g） 相对尿液尿酸（mg/200 g） 相对排便量（g/200 g） W0 W1 W1-W0 W0 W1 W1-W0 W0 W1 W1-W0 对照组 29.9 ± 5.5 24.4 ± 2.5 −5.5 ± 4.5 37.6 ± 18.4 32.0 ± 7.2 −5.6 ± 19.0 8.2 ± 1.0 7.4 ± 1.3 −0.8 ± 1.3 10.5 g/L 46.5 ± 7.7 35.7 ± 4.9 −10.8 ± 12.3 44.1 ± 20.2 23.7 ± 7.7 −20.4 ± 19.0 10.4 ± 2.6 12.0 ± 1.7 1.6 ± 3.0 5.25 g/L 33.6 ± 3.2 34.1 ± 5.1 0.5 ± 6.6 34.2 ± 17.6 28.4 ± 14.1 −5.8 ± 17.8 7.8 ± 1.1 11.0 ± 1.7 3.2 ± 2.1 2.625 g/L 38.6 ± 2.3 31.5 ± 8.3 −7.0 ± 8.3 72.0 ± 16.1 20.2 ± 9.3 −51.8 ± 23.6 7.2 ± 0.9 7.4 ± 0.9 0.2 ± 1.1 F 7.89 6.91 7.2 P 0.00* 0.00* 0.00* 与对照组比较，*P < 0.05。
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表 2 实验前后多种指标用体重校正后[（
$ \bar x \pm s $ ），n = 6] （2）Table 2. Various indexes were adjusted by weight before and after the experimen[（
$ \bar x \pm s $ ），n = 6]（2）项目 相对粪便尿酸（mg/200 g） 相对尿酸排泄总量（mg/200 g） 相对进食量（g/200 g） W0 W1 W1-W0 W0 W1 W1-W0 W0 W1 W1-W0 对照组 1.2 ± 0.7 1.3 ± 0.3 0.1 ± 0.9 38.8 ± 18.6 33.3 ± 7.0 −5.5 ± 18.8 18.4 ± 3.4 17.0 ± 0.7 −1.5 ± 3.2 10.5 g/L 2.2 ± 1.5 3.8 ± 1.3 1.6 ± 1.5 46.3 ± 19.3 27.5 ± 7.7 −18.8 ± -5.6 21.2 ± 2.7 19.1 ± 2.7 −2.1 ± 2.1 5.25 g/L 1.0 ± 0.5 1.6 ± 0.5 0.6 ± 0.4 39.1 ± 17.6 31.7 ± 13.9 −7.4 ± 17.4 20.7 ± 3.3 20.9 ± 1.4 0.2 ± 3.1 2.625 g/L 1.2 ± 0.4 0.8 ± 0.3 −0.4 ± 0.6 59.8 ± 24.8 49.4 ± 15.7 −10.3 ± -9.8 20.4 ± 1.1 18.8 ± 0.7 −1.6 ± 0.8 F 6.47 0.62 2.11 P 0.00* 0.68 0.09 与对照组比较，*P < 0.05。
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表 2 实验前后多种指标用体重校正后[（
$ \bar x \pm s $ ），n = 6] （3）Table 2. Various indexes were adjusted by weight Before and after the experiment[（
$ \bar x \pm s $ ），n = 6] （3）项目 相对饮水量（mL/200 g） W0 W1 W1-W0 对照组 52.2 ± 4.5 46.4 ± 6.3 −5.8 ± 4.1 10.5 g/L 72.5 ± 12.0 56.6 ± 10.6 −15.9 ± 13.0 5.25 g/L 53.5 ± 5.7 55.5 ± 9.9 2.0 ± 12.8 2.625 g/L 61.2 ± 3.9 56.9 ± 6.8 −4.3 ± 5.9 F 7.84 P 0.00* 与对照组比较，*P < 0.05。
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表 3 实验前后大鼠肾功能变化[（
$\bar x \pm s $ ），n = 6]Table 3. Changes of renal function indexes before and after treatment [（
$\bar x \pm s $ ），n = 6]项目 血肌酐浓度（µmol/L） 尿素氮浓度（mmol/L） W0 W1 W1-W0 W0 W1 W1-W0 对照组 32.2 ± 13.1 55.1 ± 17.7 22.9 ± 22.4 4.5 ± 1.9 4.9 ± 2.2 0.4 ± 2.2 5.25 g/L 33.1 ± 21.1 38.1 ± 18.9 5.0 ± 7.3 6.5 ± 0.9 3.7 ± 1.8 −2.8 ± 1.7 2.625 g/L 56.0 ± 14.5 43.2 ± 11.7 −12.8 ± 20.8 5.5 ± 0.6 5.4 ± 0.7 −0.1 ± 0.6 F 0.58 6.14 P 0.01* 0.01* 与对照组比较，*P < 0.05。
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[1] 叶佩玉,赵小元,闫银坤,等. 儿童高尿酸血症与心血管代谢异常发生风险[J]. 中华流行病学杂志,2021,42(3):433-439. doi: 10.3760/cma.j.cn112338-20200825-01094 [2] 王诗涵,袁涛. 儿童及青少年高尿酸血症和痛风的危险因素、病因及诊治策略[J]. 中华临床营养杂志,2021,29(3):163-170. doi: 10.3760/cma.j.cn115822-20210225-00043 [3] 徐璧云. 尿酸高:“三高”以外的“第四高”[J]. 家庭医药,2014,13(6):20-21. [4] 金剑. 高尿酸血症 危险的第四高[J]. 江苏卫生保健,2016,18(23):23. [5] 刘杨从,李妍,张耕. 18例苯溴马隆不良反应/事件分析[J]. 中国医院药学杂志,2016,36(6):507-510. doi: 10.13286/j.cnki.chinhosppharmacyj.2016.06.20 [6] 朱飞燕,孟群. 苯溴马隆致重度药物性肝损伤1例[J]. 肝脏,2017,22(10):973-974. doi: 10.3969/j.issn.1008-1704.2017.10.036 [7] 潘鑫,谢攀,常欢,等. 别嘌醇过敏可能成为肾衰竭的免疫学转机吗?[J]. 免疫学杂志,2022,38(1):88-92. [8] 陈一萍,张劼,周嘉,等. 别嘌醇药物不良反应风险因素研究进展[J]. 广西医科大学学报,2019,36(1):137-141. [9] 赵德杰,解广东,乔全来,等. 聚乙二醇4000治疗便秘的研究进展[J]. 中国中西医结合外科杂志,2018,24(5):659-662. doi: 10.3969/j.issn.1007-6948.2018.05.033 [10] 余炳取,侯陈凤,陈佳圆,等. 揿针、聚乙二醇4000散联合生物反馈疗法治疗功能性便秘临床研究[J]. 新中医,2020,52(2):130-133. [11] Ichijima R,Suzuki S,Esaki M,et al. Efficacy of macrogol 4000 plus electrolytes in bowel preparation for colonoscopy in patients with chronic constipation[J]. BMC Gastroenterology,2021,21(1):387. doi: 10.1186/s12876-021-01976-2 [12] Yu Y,Zhang N,Dong X,et al. Uricase-deficient rat is generated with CRISPR/Cas9 technique[J]. PeerJ,2020,8(4):8971. [13] 张谭畅,闵红燕,刘晓园. 非布司他对比别嘌醇在治疗痛风中不良反应的发生率[J]. 北方药学,2020,17(5):152-153. doi: 10.3969/j.issn.1672-8351.2020.05.113 [14] 郭钦惠,方宏,陈俊文,等. 非布司他药物相关不良反应文献分析[J]. 中国医学创新,2020,17(22):104-107. doi: 10.3969/j.issn.1674-4985.2020.22.027 [15] 钟燕,姜怡雯,蒋娅莉,等. 非布司他心脏不良反应信号的数据挖掘和分析[J]. 中国药房,2022,33(2):225-229. doi: 10.6039/j.issn.1001-0408.2022.02.16 [16] Hosomi A,Nakanishi T,Fujita T,et al. Extra-renal elimination of uric acid via intestinal efflux transporter BCRP/ABCG2[J]. S. R. Singh. PLoS ONE,2012,7(2):30456. doi: 10.1371/journal.pone.0030456 [17] Kelly S J,Delnomdedieu M,Oliverio M I,et al. Diabetes insipidus in uricase-deficient mice:A model for evaluating therapy with poly(ethylene glycol)-modified uricase[J]. Journal of the American Society of Nephrology:JASN,2001,12(5):1001-1009. doi: 10.1681/ASN.V1251001 [18] Lyseng-Williamson K A. Macrogol (polyethylene glycol) 4000 without electrolytes in the symptomatic treatment of chronic constipation:A profile of its use[J]. Drugs & Therapy Perspectives:For Rational Drug Selection and Use,2018,34(7):300-310. [19] 关向阳,李彩霞. 聚乙二醇4000联合麻仁软胶囊治疗儿童便秘的临床疗效分析[J]. 中国现代药物应用,2021,15(10):157-159. doi: 10.14164/j.cnki.cn11-5581/r.2021.10.059 [20] 林存侠,罗建平. 成人功能性便秘经聚乙二醇4000治疗效果及安全性分析[J]. 临床研究,2018,26(1):108-110. doi: 10.3969/j.issn.1004-8650.2018.01.056 [21] Yun Y,Yin H,Gao Z,et al. Intestinal tract is an important organ for lowering serum uric acid in rats[J]. G. Kunze. PLOS ONE,2017,12(12):0190194. doi: 10.1371/journal.pone.0190194 [22] 范楠,段为钢,云宇. 雄性Kunming-DY大鼠血尿酸水平的主要影响因素[J]. 云南中医学院学报,2020,43(6):12-17. doi: 10.19288/j.cnki.issn.1000-2723.2020.06.003 [23] Nakatochi M,Kanai M,Nakayama A,et al. Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals[J]. Communications Biology,2019,2(1):115. doi: 10.1038/s42003-019-0339-0 [24] Meng J,Lv Q,Sui A,et al. Hyperuricemia induces lipid disturbances by upregulating the CXCL-13 pathway[J]. American Journal of Physiology. Gastrointestinal and Liver Physiology,2022,322(2):256-267. doi: 10.1152/ajpgi.00285.2021 [25] Matsuo H,Ishikawa E,Machida H,et al. Efficacy of xanthine oxidase inhibitor for chronic kidney disease patients with hyperuricemia[J]. Clinical and Experimental Nephrology,2020,24(4):307-313. doi: 10.1007/s10157-019-01829-z -
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