Simiaowan Up-regulates Intestinal ABCG2 Expression to Promote Intestinal Uric Acid Excretion in Hyperuricemia Rats

ZHANG Yongqi; CHEN Jiewei; YE Bowen; HAO Zehan; DAI Hao

doi:10.13422/j.cnki.syfjx.20221601

您当前的位置：

首页 >

文章列表页 >

Simiaowan Up-regulates Intestinal ABCG2 Expression to Promote Intestinal Uric Acid Excretion in Hyperuricemia Rats

更新时间：2022-10-18

- Simiaowan Up-regulates Intestinal ABCG2 Expression to Promote Intestinal Uric Acid Excretion in Hyperuricemia Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 22, Pages: 33-39(2022)
- 作者机构：
  
  1.上海中医药大学，上海 201203
  2.上海中医药大学附属光华医院，上海 200052
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20221601
  CLC： R2-0;R22;R285.5;R289;R33
- Received：25 April 2022，
  
  Published Online：03 August 2022，
  
  Published：20 November 2022
- 稿件说明：
移动端阅览
张永琪,陈杰伟,叶博闻等.四妙丸上调高尿酸血症大鼠小肠ABCG2表达促进肠道尿酸排泄的作用[J].中国实验方剂学杂志,2022,28(22):33-39.

ZHANG Yongqi,CHEN Jiewei,YE Bowen,et al.Simiaowan Up-regulates Intestinal ABCG2 Expression to Promote Intestinal Uric Acid Excretion in Hyperuricemia Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(22):33-39.
张永琪,陈杰伟,叶博闻等.四妙丸上调高尿酸血症大鼠小肠ABCG2表达促进肠道尿酸排泄的作用[J].中国实验方剂学杂志,2022,28(22):33-39. DOI： 10.13422/j.cnki.syfjx.20221601.

ZHANG Yongqi,CHEN Jiewei,YE Bowen,et al.Simiaowan Up-regulates Intestinal ABCG2 Expression to Promote Intestinal Uric Acid Excretion in Hyperuricemia Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(22):33-39. DOI： 10.13422/j.cnki.syfjx.20221601.

摘要

目的

研究四妙丸对高尿酸血症大鼠小肠三磷酸腺苷结合盒转运蛋白G2（ABCG2）表达和肠道尿酸排泄的影响。

方法

48只雄性SD大鼠随机分为正常组、模型组、苯溴马隆组（4.7 mg·kg

-1

）和四妙丸高、中、低剂量组（2 260.6、1 130.3、565.2 mg·kg

-1

），每组8只。以氧嗪酸钾和次黄嘌呤制备高尿酸血症模型，连续21 d。第8天予相应药物干预，1次/d，持续14 d。第21天处死大鼠，检测血尿酸、肠道尿酸、血肌酐、血尿素氮等指标，以蛋白免疫印迹法（Western blot）检测大鼠小肠ABCG2蛋白表达，实时荧光定量聚合酶链式反应（Real-time PCR）检测小肠ABCG2 mRNA表达，免疫组化法检测小肠ABCG2蛋白表达和定位。

结果

与正常组比较，模型组血尿酸、血肌酐、血尿素氮显著升高（

0.01）；与模型组比较，四妙丸各剂量组和苯溴马隆组大鼠血尿酸水平均显著降低（

0.01），四妙丸中、低剂量组肠道尿酸明显升高（

0.05，

0.01），苯溴马隆组血肌酐显著升高（

0.01），低剂量组血尿素氮明显降低（

0.05），四妙丸低剂量组与苯溴马隆组血尿酸比较差异无统计学意义。Western blot结果显示，与正常组比较，模型组ABCG2蛋白表达明显下降（

0.05）；与模型组比较，四妙丸中、低剂量组ABCG2蛋白表达水平明显升高（

0.05，

0.01），四妙丸高剂量组及苯溴马隆组升高但差异无统计学意义。Real-time PCR分析显示，与正常组比较，模型组ABCG2 mRNA表达差异无统计学意义；与模型组比较，四妙丸中、低剂量组ABCG2 mRNA表达明显升高（

0.05）。免疫组化显示，ABCG2蛋白主要分布于肠绒毛，与正常组比较，模型组ABCG2蛋白表达差异无统计学意义；与模型组比较，四妙丸各剂量组ABCG2蛋白表达明显升高（

0.05）。

结论

四妙丸可显著降低高尿酸血症大鼠血尿酸，其中低剂量四妙丸具有与苯溴马隆等效的降尿酸作用，同时可保护肾功能，其机制可能与上调肠道ABCG2表达促进肠道尿酸排泄有关。

Abstract

Objective

To observe the effect of Simiaowan on the intestinal ATP-binding cassette superfamily G （White） member 2 （ABCG2） expression and the intestinal uric acid excretion in hyperuricemia rats.

Method

A total of 48 SD male rats were randomized into the normal， model， benzbromarone （4.7 mg·kg

-1

）， and high-， medium-， low-dose Simiaowan groups （2 260.6， 1 130.3， 565.2 mg·kg

-1

， respectively）， with 8 rats in each group. Potassium oxonate and hypoxanthine was employed to induce hyperuricemia in rats （21 days）. On the 8

day， administration began （once a day for 14 days）. Rats were killed on the 21

day， and serum uric acid， serum creatinine， blood urea nitrogen， and intestinal uric acid were detected. The protein expression of ABCG2 in the small intestine was detected by Western blot. The ABCG2 protein expression and localization in intestinal tissues were determined by immunohistochemistry. The ABCG2 mRNA expression in small intestine was measured by quantitative real-time PCR.

Result

The levels of serum uric acid， serum creatinine， and blood urea nitrogen in the model group were higher than those in the normal group （

0.01）. Low level of serum uric acid in the three Simiaowan groups and benzbromarone group （

0.01）， high level of intestinal uric acid in medium-dose and low-dose Simiaowan groups （

0.05，

0.01）， high level of serum creatinine in benzbromarone group （

0.01）， and low level of blood urea nitrogen in low-dose Simiaowan group （

0.05） were observed as compared with those in the model group. Serum uric acid showed insignificant difference between the low-dose Simiaowan group and benzbromarone group. The expression of ABCG2 protein in the model group was lower than that in the normal group （

0.05）. The expression of ABCG2 protein in the medium-dose and low-dose Simiaowan groups （

0.05，

0.01）， the high-dose Simiaowan group， and benzbromarone group increased as compared with that in the model group. ABCG2 mRNA expression was insignificantly different between the model group and the normal group， while the expression in the medium-dose and low-dose Simiaowan groups was higher than that in the model group （

0.05）. ABCG2 protein was mainly distributed in intestinal villi， and ABCG2 protein expression demonstrated no significant difference between the model group and the normal group. The ABCG2 protein expression in the three Simiaowan groups increased as compared with that in the model group （

0.05）.

Conclusion

Simiaowan can significantly reduce the serum uric acid level in hyperuricemia rats. Particularly， the low-dose Simiaowan shows similar efficacy to benzbromarone in lowering uric acid and protects renal function. The mechanism is the likelihood that it up-regulates intestinal ABCG2 expression to promote intestinal excretion of uric acid.

关键词

Keywords

references

丁小强，冯哲，倪兆慧，等 . 中国肾脏疾病高尿酸血症诊治的实践指南（2017版）［J］. 中华医学杂志， 2017 ， 97 （ 25 ）： 1927 - 1936 .

KUWABARA M ， HISATOME I ， NIWA K ， et al . Uric acid is a strong risk marker for developing hypertension from prehypertension： A 5-year Japanese cohort study ［J］. Hypertension ， 2018 ， 71 （ 1 ）： 78 - 86 .

TAO M ， PI X ， MA X ， et al . Relationship between serum uric acid and clustering of cardiovascular disease risk factors and renal disorders among Shanghai population： A multicentre and cross-sectional study ［J］. BMJ Open ， 2019 ， 9 （ 3 ）： e025453 .

SHARAF E L ， SALEM M M ， ABDULAZIM D O . Uric acid in the pathogenesis of metabolic，renal，and cardiovascular diseases： A review ［J］. J Adv Res ， 2017 ， 8 （ 5 ）： 537 - 548 .

李林，朱小霞，戴宇翔，等 . 中国高尿酸血症相关疾病诊疗多学科专家共识［J］. 中华内科杂志， 2017 ， 56 （ 3 ）： 235 - 248 .

SO A ， THORENS B . Uric acid transport and disease ［J］. J Clin Invest ， 2010 ， 120 （ 6 ）： 1791 - 1799 .

中国医师协会中西医结合医师分会内分泌与代谢病学专业委员会 . 高尿酸血症和痛风病证结合诊疗指南（2021-01-20）［J］. 世界中医药， 2021 ， 16 （ 2 ）： 183 - 189 .

XU L ， SHI Y ， ZHUANG S ， et al . Recent advances on uric acid transporters ［J］. Oncotarget ， 2017 ， 8 （ 59 ）： 100852 - 100862 .

XU X ， LI C ， ZHOU P ， et al . Uric acid transporters hiding in the intestine ［J］. Pharm Biol ， 2016 ， 54 （ 12 ）： 3151 - 3155 .

TIN A ， MARTEN J ， HALPERIN KUHNS V L ， et al . Target genes，variants，tissues and transcriptional pathways influencing human serum urate levels ［J］. Nat Genet ， 2019 ， 51 （ 10 ）： 1459 - 1474 .

HOQUE K M ， DIXON E E ， LEWIS R M ， et al . The ABCG2 Q141K hyperuricemia and gout associated variant illuminates the physiology of human urate excretion ［J］. Nat Commun ， 2020 ， 11 （ 1 ）： 2767 .

ICHIDA K ， MATSUO H ， TAKADA T ， et al . Decreased extra-renal urate excretion is a common cause of hyperuricemia ［J］. Nat Commun ， 2012 ， 3 ： 764 .

YE X ， WU J ， TANG K ， et al . Benzbromarone as a possible cause of acute kidney injury in patients with urolithiasis： Two case reports ［J］. Medicine （Baltimore）， 2019 ， 98 （ 15 ）： e15214 .

FUJITA K ， ICHIDA K . ABCG2 as a therapeutic target candidate for gout ［J］. Expert Opin Ther Targets ， 2018 ， 22 （ 2 ）： 123 - 129 .

HU Q H ， JIAO R Q ， WANG X ， et al . Simiaowan ameliorates urate underexcretion and renal dysfunction in hyperuricemic mice ［J］. J Ethnopharmacol ， 2010 ， 128 （ 3 ）： 685 - 692 .

吴丽 . 利湿活血方对高尿酸血症大鼠降尿酸作用及对尿酸转运体的影响［D］. 北京：北京中医药大学， 2018 ： 90 - 91 .

YUN Y ， YIN H ， GAO Z ， et al . Intestinal tract is an important organ for lowering serum uric acid in rats ［J］. PLoS One ， 2017 ， 12 （ 12 ）： e0190194 .

魏瑶，吴珍，杨玉姣，等 . 加味四妙丸对高尿酸血症小鼠的降尿酸及肾脏保护作用研究［J］. 中药材， 2021 ， 44 （ 9 ）： 2184 - 2188 .

CLEOPHAS M C ， JOOSTEN L A ， STAMP L K ， et al . ABCG2 polymorphisms in gout： Insights into disease susceptibility and treatment approaches ［J］. Pharmgenomics Pers Med ， 2017 ， 10 ： 129 - 142 .

王星，薛宁，李洪雷，等 . 防己黄芪汤对高尿酸血症小鼠降尿酸及肾保护作用机制的研究［J］. 中国中药杂志， 2020 ， 45 （ 21 ）： 5248 - 5255 .

YANO H ， TAMURA Y ， KOBAYASHI K ， et al . Uric acid transporter ABCG2 is increased in the intestine of the 5/6 nephrectomy rat model of chronic kidney disease ［J］. Clin Exp Nephrol ， 2014 ， 18 （ 1 ）： 50 - 55 .

TAKADA T ， ICHIDA K ， MATSUO H ， et al . ABCG2 dysfunction increases serum uric acid by decreased intestinal urate excretion ［J］. Nucleosides Nucleotides Nucleic Acids ， 2014 ， 33 （ 4/6 ）： 275 - 281 .

张志明，高碧珍，齐张，等 . 基于肠道上皮细胞相关转运子探讨四妙散对高尿酸血症小鼠的祛湿机制［J］. 风湿病与关节炎， 2020 ， 9 （ 1 ）： 1 - 4，20 .

VON WEDEL-PARLOW M ， WÖLTE P ， GALLA H J . Regulation of major efflux transporters under inflammatory conditions at the blood-brain barrier in vitro ［J］. J Neurochem ， 2009 ， 111 （ 1 ）： 111 - 118 .

LU X ， CHEN M ， SHEN J ， et al . IL-1 β functionally attenuates ABCG2 and PDZK1 expression in HK-2 cells partially through NF- κ B activation ［J］. Cell Biol Int ， 2019 ， 43 （ 3 ）： 279 - 289 .

曾丽莹，邓伊健，陈洁瑜，等 . 基于网络药理学和分子对接探讨四妙丸治疗高尿酸血症的作用机制［J］. 南方医科大学学报， 2021 ， 41 （ 4 ）： 579 - 587 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Mechanisms of Intestinal Microecology in Hyperuricemia and Traditional Chinese Medicine Intervention：A Review

Treatment of Hyperuricemia and Gouty Arthritis by Buyang Huanwu Tongfeng Decoction via Inhibition of PPAR-γ/NF-κB/AGEs/RAGE Pathway Based on Network Pharmacology

Exploring Efficacy and Mechanism of Saffron Floral Bio-residues for Treatment of Hyperuricemia Combined with Gouty Arthritis Based on Compound Compatibility Environment

Shenling Baizhusan Improves Spermatogenesis in Hyperuricemia Oligoasthenospermia Mice by Regulating Nrf2/ARE Pathway

Clinical Effect of Erchentang and Bixie Fenqingyin Combined on Patients with Acute Cerebral Infarction with Hyperuricemia with Syndrome of Phlegm and Blood Stasis Blocking Collaterals

Related Author

FAN Mingyuan

YUAN Jiuzhu

XIE Hongyan

ZHANG Sai

YAO Qiyuan

HE Luqi

FU Qingqing

GAO Hong

Related Institution

TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province， Chengdu University of TCM

Hospital of Chengdu University of Traditional Chinese Medicine （TCM）

Shanxi University of Chinese Medicine

Prescription and Drug Compatibility and Function Research Laboratory Supported by Shanxi Provincial Administration of TCM，Shanxi University of Chinese Medicine

Experimental Research Center，China Academy of Chinese Medical Sciences

AI问答

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰