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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