研究报告

壳寡糖复合固体饮料对高尿酸血症小鼠的降尿酸作用研究

  • 庄林 ,
  • 操俊 ,
  • 李月婵 ,
  • 王佳丽 ,
  • 陈列欢 ,
  • 罗学刚
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  • 1(天津科技大学 生物工程学院, 工业发酵微生物教育部重点实验室暨天津市工业微生物重点实验室,天津,300457)
    2(新优蓝健康科技有限公司,广东 广州,510530)
    3(天津市微生物代谢与发酵过程控制技术工程中心,天津,300457)
硕士研究生(罗学刚教授为通信作者,E-mail:luoxuegang@hotmail.com)

收稿日期: 2021-12-22

  修回日期: 2022-01-27

  网络出版日期: 2023-03-20

基金资助

国家重点研发计划项目(2017YFD0400303)

Effect of chitooligosaccharide compound solid beverage on reducing uric acid in hyperuricemia mice

  • ZHUANG Lin ,
  • CAO Jun ,
  • LI Yuechan ,
  • WANG Jiali ,
  • CHEN Liehuan ,
  • LUO Xuegang
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  • 1(Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, School of Bioengineering, Tianjin University of Science and Technology, Tianjin 300457, China)
    2(New Youlan Health and Technology Co. Ltd., Guangzhou 510530, China)
    3(Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China)

Received date: 2021-12-22

  Revised date: 2022-01-27

  Online published: 2023-03-20

摘要

为探究壳寡糖复合固体饮料“壳酸平”(ke suan ping,KSP)在高尿酸血症小鼠中的降尿酸及肝肾保护作用,该研究将60只昆明小鼠分为6组:阴性对照组(negative group,NC)、高尿酸血症模型组(model group,M)、低剂量KSP组(low-dose KSP group,LKSP)、中剂量KSP组(middle-dose KSP group,MKSP)、高剂量KSP组(high-dose KSP group,HKSP)、别嘌呤醇组(allopurinol group,AP)。适应性喂养1周后,通过腹腔注射氧嗪酸钾辅以灌胃酵母膏建立了高尿酸血症模型小鼠,同时更换KSP组小鼠饲料为含不同剂量KSP的饲料,AP组在造模1 h以后给药。收集小鼠血清用于尿酸、肌酐、尿素氮、黄嘌呤氧化酶的检测;收集小鼠肝、肾、肠用于苏木精-伊红染色法(hematoxylin-eosin staining,HE染色)和q-PCR。结果显示,与M组相比,KSP可以降低高尿酸血症小鼠血清尿酸、肌酐、尿素氮、黄嘌呤氧化酶活性,缓解高尿酸血症小鼠肝肾损伤,调节GLUT9、URAT1、ABCG2蛋白转录水平的表达。研究证明KSP可以通过降低黄嘌呤氧化酶的活性促进尿酸排泄等发挥降尿酸作用。

本文引用格式

庄林 , 操俊 , 李月婵 , 王佳丽 , 陈列欢 , 罗学刚 . 壳寡糖复合固体饮料对高尿酸血症小鼠的降尿酸作用研究[J]. 食品与发酵工业, 2023 , 49(4) : 97 -102 . DOI: 10.13995/j.cnki.11-1802/ts.030551

Abstract

To explore the uric acid-lowering effect of chitooligosaccharide solid beverage (ke suan ping, KSP) in hyperuricemia mice, a total of 60 Kunming mice were divided into 6 groups, including a negative control group (NC), hyperuricemia model group (M), and low-dose KSP group (LKSP), middle-dose KSP group (MKSP), high-dose KSP group (HKSP), and allopurinol group (AP). After one week of adaptive feeding, hyperuricemia mice were injected with potassium oxonate and supplemented with yeast extracts. At the same time, the fodders of mice in KSP groups were changed into the forages containing KSP in different doses. The mice in the AP group were administered with PBS buffer after injection. The test lasted 21 days. Serum of mice was collected for the detection of uric acid (UA), creatinine (CR), urine urea nitrogen (BUN), and xanthine oxidase (XOD). And the mouse liver, kidney, and small intestine were collected for HE staining and q-PCR. Results showed that KSP could reduce serum UA, CR, and BUN and the activities of XOD in hyperuricemia mice, alleviate the damage of the liver and kidney in hyperuricemia mice, and regulate the mRNA expression of GLUT9, URAT1, and ABCG2. In short, KSP could reduce UA by inhibiting the activity of XOD and promoting the excretion of UA in hyperuricemia.

参考文献

[1] PUNZI L, SCANU A, GALOZZI P, et al.One year in review 2020:Gout[J].Clinical and Experimental Rheumatology, 2020, 38(5):807-821.
[2] 孙珊珊, 曲连悦, 杜荣蓉, 等.高尿酸血症药物治疗研究进展[J].中国临床药理学与治疗学, 2019, 24(5):589-594.
SUN S S, QU L Y, DU R R, et al.Research progress on drug therapy of hyperuricemia[J].Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(5):589-594.
[3] 杨靖亚, 郑雯静, 李诗怡.壳寡糖的制备及生物活性研究进展[J].国际药学研究杂志, 2020, 47(7):502-507.
YANG J Y, ZHENG W J, LI S Y.Preparation and bioactivity of chitosan oligosaccharide:Research advances[J].Journal of International Pharmaceutical Research, 2020, 47(7):502-507.
[4] 孙晨松, 王硕, 王一迪, 等.壳寡糖功能特性研究进展[J].食品工业科技, 2021, 42(16):438-446.
SUN C S, WANG S, WANG Y D, et al.Research progress on the functional characteristics of chitooligosaccharides[J].Science and Technology of Food Industry, 2021, 42(16):438-446.
[5] 刘洋, 韩宝芹, 刘万顺, 等.壳寡糖对酵母联合腺嘌呤致高尿酸血症小鼠的治疗作用[J].中国海洋大学学报(自然科学版), 2009,39(S1):143-146.
LIU Y, HAN B Q, LIU W S, et al.Effects of chitooligosaccharide on the mice hyperuricemia model induced by yeast and adenine[J].Periodical of Ocean University of China, 2009,39(S1):143-146.
[6] LI R R, TAN Y F, LI Y X, et al.Effects of tart cherry powder on serum uric acid in hyperuricemia rat model[J].Evidence-Based Complementary and Alternative Medicine ECAM, 2020, 2020:1454305.
[7] ZHANG Y L, SU H, ZHANG J, et al.The effects of ginsenosides and anserine on the up-regulation of renal aquaporins 1-4 in hyperuricemic mice[J].The American Journal of Chinese Medicine, 2019, 47(5):1 133-1 147.
[8] LIANG D L, YONG T Q, DIAO X, et al.Hypouricaemic and nephroprotective effects of Poria cocos in hyperuricemic mice by up-regulating ATP-binding cassette super-family G member 2[J].Pharmaceutical Biology, 2021, 59(1):275-284.
[9] WANG Z, CUI T, CI X Y, et al.The effect of polymorphism of uric acid transporters on uric acid transport[J].Journal of Nephrology, 2019, 32(2):177-187.
[10] LU Y H, CHANG Y P, LI T, et al.Empagliflozin attenuates hyperuricemia by upregulation of ABCG2 via AMPK/AKT/CREB signaling pathway in type 2 diabetic mice[J].International Journal of Biological Sciences, 2020, 16(3):529-542.
[11] KUBOTA M.Hyperuricemia in children and adolescents:Present knowledge and future directions[J].Journal of Nutrition and Metabolism, 2019, 2019:3480718.
[12] 王爱华, 金玥, 吴越, 等.具有黄嘌呤氧化酶抑制作用的中药及中成药治疗高尿酸血症研究进展[J].天津中医药, 2019, 36(12):1 241-1 245.
WANG A H, JIN Y, WU Y, et al.Research progress on treatment of gout by xanthine oxidase inhibitor in traditional Chinese medicine[J].Tianjin Journal of Traditional Chinese Medicine, 2019, 36(12):1 241-1 245.
[13] GUO Y J, YU Y N, LI H L, et al.Inulin supplementation ameliorates hyperuricemia and modulates gut microbiota in Uox-knockout mice[J].European Journal of Nutrition, 2021, 60(4):2 217-2 230.
[14] CHEN Y Y, ZHAO Z, LI Y M, et al.Baicalein alleviates hyperuricemia by promoting uric acid excretion and inhibiting xanthine oxidase[J].Phytomedicine, 2021, 80:153374.
[15] WAN Y, QIAN J, LI Y Z, et al.Inhibitory mechanism of xanthine oxidase activity by caffeoylquinic acids in vitro[J].International Journal of Biological Macromolecules, 2021, 184:843-856.
[16] ZACCHERINI G, WEISS E, MOREAU R.Acute-on-chronic liver failure:Definitions, pathophysiology and principles of treatment[J].JHEP Reports, 2021, 3(1):100176.
[17] YAN C Y, OUYANG S H, WANG X, et al.Celastrol ameliorates Propionibacterium acnes/LPS-induced liver damage and MSU-induced gouty arthritis via inhibiting K63 deubiquitination of NLRP3[J].Phytomedicine, 2021, 80:153398.
[18] ZHAO M, LIU S Y, WANG C S, et al.Mesenchymal stem cell-derived extracellular vesicles attenuate mitochondrial damage and inflammation by stabilizing mitochondrial DNA[J].ACS Nano, 2021, 15(1):1 519-1 538.
[19] ALJOBAILY N, VIERECKL M J, HYDOCK D S, et al.Creatine alleviates doxorubicin-induced liver damage by inhibiting liver fibrosis, inflammation, oxidative stress, and cellular senescence[J].Nutrients, 2020, 13(1):41.
[20] JOO H J, KIM G R, CHOI D W, et al.Uric acid level and kidney function:A cross-sectional study of the Korean national health and nutrition examination survey (2016—2017)[J].Scientific Reports, 2020, 10:21672.
[21] TOYODA Y, KAWAMURA Y, NAKAYAMA A, et al.Substantial anti-gout effect conferred by common and rare dysfunctional variants of URAT1/SLC22A12[J].Rheumatology, 2021, 60(11):5 224-5 232.
[22] LI G T, HAN L F, MA R C, et al.Glucocorticoids increase renal excretion of urate in mice by downregulating urate transporter 1[J].Drug Metabolism and Disposition:the Biological Fate of Chemicals, 2019, 47(11):1 343-1 351.
[23] MATSUBAYASHI M, SAKAGUCHI Y M, SAHARA Y, et al.27-Hydroxycholesterol regulates human SLC22A12 gene expression through estrogen receptor action[J].The FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 2021, 35(1):e21262.
[24] WANG Q T, JIANG Y J, LUO X G, et al.Chitooligosaccharides modulate glucose-lipid metabolism by suppressing SMYD3 pathways and regulating gut microflora[J].Marine Drugs, 2020, 18(1):69.
[25] LUO X G, XI T, GUO S, et al.Effects of SMYD3 overexpression on transformation, serum dependence, and apoptosis sensitivity in NIH3T3 cells[J].IUBMB Life, 2009, 61(6):679-684.
[26] LUO X G, DING Y, ZHOU Q F, et al.SET and MYND domain-containing protein 3 decreases sensitivity to dexamethasone and stimulates cell adhesion and migration in NIH3T3 cells[J].Journal of Bioscience and Bioengineering, 2007, 103(5):444-450.
[27] KIM H, HEO K, KIM J H, et al.Requirement of histone methyltransferase SMYD3 for estrogen receptor-mediated transcription[J].Journal of Biological Chemistry, 2009, 284(30):19 867-19 877.
[28] RAFIULLAH M, SIDDIQUI K, AL-RUBEAAN K.Association between serum uric acid levels and metabolic markers in patients with type 2 diabetes from a community with high diabetes prevalence[J].International Journal of Clinical Practice, 2020, 74(4):e13466.
[29] CHEN Y Y, ZHAO Z, LI Y M, et al.Characterizations of the urate transporter, GLUT9, and its potent inhibitors by patch-clamp technique[J].SLAS Discovery, 2021, 26(3):450-459.
[30] LI L, LI Y M, LUO J, et al.Resveratrol, a novel inhibitor of GLUT9, ameliorates liver and kidney injuries in a D-galactose-induced ageing mouse model via the regulation of uric acid metabolism[J].Food & Function, 2021, 12(18):8 274-8 287.
[31] ZHANG Y, TAN X H, LIN Z, et al.Fucoidan from Laminaria japonica inhibits expression of GLUT9 and URAT1 via PI3K/Aat, JNK and NF-κB pathways in uric acid-exposed HK-2 cells[J].Marine Drugs, 2021, 19(5):238.
[32] 姬志祥, 蓝常贡.尿酸盐转运蛋白在痛风中的多态性和治疗相关性[J].中国组织工程研究, 2021, 25(8):1 290-1 298.
JI Z X, LAN C G.Polymorphism of urate transporter in gout and its correlation with gout treatment[J].Chinese Journal of Tissue Engineering Research, 2021, 25(8):1 290-1 298.
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