Resveratrol improves renal inflammatory injury in exhaustive exercise rats by regulating NOD-like receptor protein 3 inflammasome

Fang LI; Jianmin CAO; Pengfei ZHAI; Jianshe WANG; Da HONG

doi:10.16016/j.2097-0927.202110114

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Resveratrol improves renal inflammatory injury in exhaustive exercise rats by regulating NOD-like receptor protein 3 inflammasome

Basic Medicine | 更新时间：2026-01-09

- Resveratrol improves renal inflammatory injury in exhaustive exercise rats by regulating NOD-like receptor protein 3 inflammasome
- Journal of Army Medical University Vol. 44, Issue 12, Pages: 1229-1236(2022)
- 作者机构：
  
  1.453007 河南新乡，河南师范大学体育学院
  2.100084 北京，北京体育大学运动人体科学学院
- 作者简介：
- 基金信息：
  
  the Project of Key Science and Technology Research and Development of Henan Province(212102310261)
- DOI：10.16016/j.2097-0927.202110114
  CLC： R285.5;R692.3;R873.01
- Received：21 October 2021，
  
  Revised：2022-01-16，
  
  Published：30 June 2022
- 稿件说明：
移动端阅览
Fang LI, Jianmin CAO, Pengfei ZHAI, et al. Resveratrol improves renal inflammatory injury in exhaustive exercise rats by regulating NOD-like receptor protein 3 inflammasome[J]. Journal of Army Medical University, 2022, 44(12): 1229-1236.
DOI：

Fang LI, Jianmin CAO, Pengfei ZHAI, et al. Resveratrol improves renal inflammatory injury in exhaustive exercise rats by regulating NOD-like receptor protein 3 inflammasome[J]. Journal of Army Medical University, 2022, 44(12): 1229-1236. DOI： 10.16016/j.2097-0927.202110114.

摘要

目的

探讨白藜芦醇通过调节NOD样受体蛋白3(NOD-like receptor protein 3，NLRP3)炎性小体对力竭运动大鼠肾组织炎症损伤的改善作用。

方法

将36只SD雄性大鼠按随机数字表法分为对照组(Con组，

=8)、白藜芦醇组(Rsv组，

=8)、力竭运动组(Ex组，

=10)和力竭运动+白藜芦醇组(Ex+Rsv组，

=10)。Ex组和Ex+Rsv组进行4周力竭跑台运动。Rsv组和Ex+Rsv组每天灌胃白藜芦醇，剂量为50 mg/kg。最后1次运动24 h后取材，分别取血、尿和肾组织以备检测，全自动分析仪检测血清肌酐(serum creatinine，Scr)、尿素氮(blood urea nitrogen，BUN)水平；ELISA检测尿中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinaseassociated lipocalin，NGAL)和肾损伤分子-1 (kidney injury molecule-1，KIM-1)以及肾组织IL-1β、IL-18、TNF-α、IL-6水平；HE染色观察肾组织形态结构变化；Western blot检测肾组织NLRP3、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein，ASC)和cleaved caspase-1、IL-1β和IL-18蛋白表达；免疫荧光双染观察NLRP3和ASC在肾小管的共定位。

结果

力竭运动组大鼠血清指标Scr及BUN、尿液指标KIM-1和NGAL水平均比对照组显著升高(

0.01)，肾组织HE染色显示存在肾组织损伤；力竭运动组大鼠肾组织NLRP3、ASC、cleaved caspase-1、IL-1β和IL-18蛋白表达均显著升高(

0.01)；白藜芦醇补充显著降低了力竭运动大鼠肾组织NLRP3炎性小体蛋白表达(

0.05)，改善其肾组织形态，降低肾组织炎症因子浓度(

0.05)。

结论

白藜芦醇可有效改善力竭运动大鼠肾组织炎症损伤，其机制可能与白藜芦醇抑制大鼠肾脏NLRP3炎性小体的过度激活有关。

Abstract

Objective

To explore the ameliorative effects of resveratrol on renal inflammation in rats after exhaustive exercise by regulating NOD-like receptor protein 3 (NLRP3) inflammasome.

Methods

Thirty-six male SD rats were randomly divided into 4 groups: control group (Con

=8)

resveratrol group (Rsv

=8)

exhaustive exercise group (Ex

=10)

and exhaustive exercise+resveratrol group (Ex+Rsv

=10)

and the rats in the Ex and Ex+Rsv groups underwent 4 weeks of exhaustive treadmill exercise. The Rsv and Ex+Rsv groups were given resveratrol intragastrically at a dose of 50 mg/kg per day. The serum and urine samples as well as renal tissues of rats were collected in 24 h after the last training. The serum creatinine (Scr) and blood urea nitrogen (BUN) levels were detected by automatic analyzer; ELISA was used to determine the urine neutrophil gelatinase-associated lipocalin (NGAL)

kidney injury molecule-1 (KIM-1) and the contents of IL-1β

IL-18

TNF-α and IL-6 in renal tissues; The protein expression of NLRP3

apoptosis-associated speck-like protein (ASC)

cleaved caspase-1

IL-1β and IL-18 were measured by Western blotting. In addition

the morphological and structural changes of renal tissue were observed with HE staining

and immunofluorescence staining was also performed to observe the co-localization of NLRP3 and ASC.

Results

The levels of Scr

BUN

NGAL and KIM-1 were significantly higer in the Ex group than the Con group (

0.01). HE staining showed that renal injury was observed in the rats of Ex group

and the protein expression levels of NLRP3

ASC

cleaved caspase-1

IL-1β and IL-18 were all remarkably increased (

0.01). However

resveratrol supplementation notably down-regulated the protein e

xpression of NLRP3 inflammasome (

0.05) and reduced the contents of inflammatory factors in renal tissues (

0.05)

and ameliorated pathological changes of renal tissues.

Conclusions

Resveratrol can effectively alleviate the inflammatory damage of renal tissue in rats after exhaustive exercise

and its mechanism may be related to its inhibiting NLRP3 inflammasome overactivation.

关键词

Keywords

references

VAN WIJCK K, LENAERTS K, VAN LOON L J, et al . Exercise-induced splanchnic hypoperfusion results in gut dysfunction in healthy men[J ] . PLoS One, 2011, 6(7): e22366. DOI: 10.1371/journal.pone.0022366.

CARVOUNIS C P, NISAR S, GURO-RAZUMAN S. Significance of the fractional excretion of urea in the differential diagnosis of acute renal failure[J]. Kidney Int, 2002, 62 (6): 2223-2229. DOI: 10.1046/j.1523-1755.2002.00683.x.

WOŁYNIEC W, KASPROWICZ K, GIEBUŁTOWICZ J, et al . Changes in water soluble uremic toxins and urinary acute kidney injury biomarkers after 10-and 100-km runs[J ] . Int J Environ Res Public Health, 2019, 16(21): E4153. DOI: 10.3390/ijerph16214153.

JOUFFROY R, LEBRETON X, MANSENCAL N, et al . Acute kidney injury during an ultra-distance race[J ] . PLoS One, 2019, 14(9): e0222544. DOI: 10.1371/journal.pone.0222544.

CHAWLA L S, EGGERS P W, STAR R A, et al . Acute kidney injury and chronic kidne y disease as interconnected syndromes[J ] . N Engl J Med, 2014, 371(1): 58-66. DOI: 10.1056/NEJMra1214243.

WOŁYNIEC W, KASPROWICZ K, RITA-TKACHENKO P, et al . Biochemical markers of renal hypoperfusion, hemoconcentration, and proteinuria after extreme physical exercise[J ] . Medicina (Kaunas), 2019, 55(5): E154. DOI: 10.3390/medicina55050154.

JANG M, CAI L, UDEANI G O, et al . Cancer chemopreventive activity of resveratrol, a natural product derived from grapes[J ] . Science, 1997, 275(5297): 218-220. DOI: 10.1126/science.275.5297.218.

MENG T T, XIAO D F, MUHAMMED A, et al . Anti-inflammatory action and mechanisms of resveratrol[J ] . Molecules, 2021, 26(1): E229. DOI: 10.3390/molecules26010229.

WANG N, MAO L, YANG L, et al . Resveratrol protects against early polymicrobial sepsis-induced acute kidney injury through inhibiting endoplasmic reticulum stress-activated NF-κB pathway[J ] . Oncotarget, 2017, 8(22): 36449-36461. DOI: 10.18632/oncotarget.16860.

ZAHEDI H S, JAZAYERI S, GHIASVAND R, et al . Effects of Polygonum cuspidatum containing resveratrol on inflammation in male professional basketball players[J ] . Int J Prev Med, 2013, 4(Suppl 1): S1-S4.

MACEDO R C, VIEIRA A, MARIN D P, et al . Effects of chronic resveratrol supplementation in military firefighters undergo a physical fitness test: a placebo-controlled, double blind study[J ] . Chem Biol Interact, 2015, 227: 89-95. DOI: 10.1016/j.cbi.2014.12.033.

林喜秀. 力竭运动致大鼠慢性肾损伤机制及促红细胞生成素干预研究[D]. 长沙: 湖南师范大学, 2011. DOI: 10.7666/d.y1919806.

LIN X X. Research of exhaustive exercise-induced chronic kidney injury mechanism and erythropoietin intervention in rats[D]. Changsha: Hunan Normal University, 2011. DOI: 10.7666/d.y1919806

李方, 曹建民, 王传军, 等. 白藜芦醇通过调节SIRT1/NF-κB通路减轻力竭训练致大鼠肾的炎症反应[J]. 中国生物化学与分子生物学报, 2019, 35(7): 773-779. DOI: 10.13865/j.cnki.cjbmb.2019.07.11.

LI F, CAO J M, WANG C J, et al . Resveratrol reduces renal inflammatory response induced by exhaustive exercise in rats by regulating SIRT1/NF-κB pathway[J ] . Chin J Biochem Mol Biol, 2019, 35(7): 773-779. DOI: 10.13865/j.cnki.cjbmb.2019.07.11.

王学龄. 白藜芦醇通过调节SIRT1缓解高糖刺激的肾小管上皮细胞损伤[D], 济南: 山东大学, 2017.

WANG X L. Resveratrol relieves renal tubular epithelial cell damage stimulated by high glucose by regulating SIRT1[D], Jinan: Shandong University, 2017.

BERNECKER C, SCHERR J, SCHINNER S, et al . Evidence for an exercise induced increase of TNF-α and IL-6 in marathon runners[J ] . Scand J Med Sci Sports, 2013, 23 (2): 207-214. DOI: 10.1111/j.1600-0838.2011.01372.x.

ZALDIVAR F, WANG-RODRIGUEZ J, NEMET D, et al . Constitutive pro-and anti-inflammatory cytokine and growth factor response to exercise in leukocytes[J ] . J Appl Physiol (1985), 2006, 100(4): 1124-1133. DOI: 10.1152/japplphysiol.00562.2005.

RONCAL-JIMENEZ C, LANASPA M A, JENSEN T, et al . Mechanisms by which dehydration may lead to chronic kidney disease[J ] . Ann Nutr Metab, 2015, 66(Suppl 3): 10-13. DOI: 10.1159/000381239.

郭林. 大负荷训练导致大鼠肾组织微细结构变化和分子调控机理的探讨[D]. 北京: 北京体育大学, 2005.

GUO L. Change of renal tissue micro-structure in rats resulted from load training and mechanisms of molecule regulation[D]. Beijing: Beijing Sport University, 2005.

LAMKANFI M, DIXIT V M. Mechanisms and functions of inflammasomes[J]. Cell, 2014, 157(5): 1013-1022. DOI: 10.1016/j.cell.2014.04.007.

PELLEGRINI C, FORNAI M, ANTONIOLI L, et al . Phytochemicals as novel therapeutic strategies for NLRP3 inflammasome-related neurological, metabolic, and inflammatory diseases[J ] . Int J Mol Sci, 2019, 20(12): E2876. DOI: 10.3390/ijms20122876.

XIONG W, MENG X F, ZHANG C. NLRP3 inflammasome in metabolic-associated kidney diseases: an update[J]. Front Immunol, 2021, 12: 714340. DOI: 10.3389/fimmu.2021.714340.

KIM Y G, KIM S M, KIM K P, et al . The role of inflammasome-dependent and inflammasome-independent NLRP3 in the kidney[J ] . Cells, 2019, 8(11): E1389. DOI: 10.3390/cells8111389.

LI H Y, MIAO W G, MA J F, et al . Acute exercise-induced mitochondrial stress triggers an inflammatory response in the myocardium via NLRP3 inflammasome activation with mitophagy[J ] . Oxid Med Cell Longev, 2016, 2016: 1987149. DOI: 10.1155/2016/1987149.

LIU B H, LU R R, LI H L, et al . Zhen-wu-Tang ameliorates membranous nephropathy rats through inhibiting NF-κB pathway and NLRP3 inflammasome[J ] . Phytomedi cine, 2019, 59: 152913. DOI: 10.1016/j.phymed.2019.152913.

SEO J B, CHOI Y K, WOO H I, et al . Gemigliptin attenuates renal fibrosis through down-regulation of the NLRP3 inflammasome[J ] . Diabetes Metab J, 2019, 43(6): 830-839. DOI: 10.4093/dmj.2018.0181.

HAN W B, MA Q, LIU Y L, et al . Huangkui capsule alleviates renal tubular epithelial-mesenchymal transition in diabetic nephropathy via inhibiting NLRP3 inflammasome activation and TLR4/NF-κB signaling[J ] . Phytomedicine, 2019, 57: 203-214. DOI: 10.1016/j.phymed.2018.12.021.

BAI Y, MU Q Q, BAO X L, et al . Targeting NLRP3 inflammasome in the treatment of diabetes and diabetic complications: role of natural compounds from herbal medicine[J ] . Aging Dis, 2021, 12(7): 1587-1604. DOI:10.14336/AD.2021.0318.

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