Protective effect of resveratrol against hepatic ischemia reperfusion injury in rats and its relationship with Sirt1-p53 signaling pathway

Yi GOU; Tianwu YU; Zhongrong HUANG; Leida ZHANG

doi:10.16016/j.1000-5404.201612157

您当前的位置：

首页 >

文章列表页 >

Protective effect of resveratrol against hepatic ischemia reperfusion injury in rats and its relationship with Sirt1-p53 signaling pathway

Basic Medicine | 更新时间：2026-01-09

- Protective effect of resveratrol against hepatic ischemia reperfusion injury in rats and its relationship with Sirt1-p53 signaling pathway
- Journal of Third Military Medical University Vol. 39, Issue 13, Pages: 1366-1370(2017)
- 作者机构：
  
  1.402160 重庆永川，重庆医科大学附属永川医院肝胆外科
  2.400038 重庆，第三军医大学西南医院全军肝胆外科研究所
- 作者简介：
- 基金信息：
  
  the Project of Yongchuan Hospital of Chongqing Medical University(YJQN201432)
- DOI：10.16016/j.1000-5404.201612157
  CLC： R285.5;R364.12;R657.3
- Received：22 December 2016，
  
  Revised：2017-03-22，
  
  Published：15 July 2017
- 稿件说明：
移动端阅览
Yi GOU, Tianwu YU, Zhongrong HUANG, et al. Protective effect of resveratrol against hepatic ischemia reperfusion injury in rats and its relationship with Sirt1-p53 signaling pathway[J]. Journal of Third Military Medical University, 2017, 39(13): 1366-1370.
DOI：

Yi GOU, Tianwu YU, Zhongrong HUANG, et al. Protective effect of resveratrol against hepatic ischemia reperfusion injury in rats and its relationship with Sirt1-p53 signaling pathway[J]. Journal of Third Military Medical University, 2017, 39(13): 1366-1370. DOI： 10.16016/j.1000-5404.201612157.

摘要

目的

探讨白藜芦醇(resveratrol，RES)对大鼠肝脏缺血再灌注损伤(hepatic ischemia reperfusion injury，HIRI)的保护作用及其具体分子机制。

方法

雄性6周龄SD大鼠20只随机数字法分为4组(

=5)：假手术组、缺血再灌注组、RES预处理组、RES预处理+抑制剂组。建立大鼠肝脏70%热缺血再灌注模型(缺血1 h，再灌注6 h)，并提前1 h给予RES及Sirt1抑制剂(EX527)。建模后检测血清标本中ALT活力及肝组织SOD活性，HE染色观察肝组织病理损伤，TUNEL法检测肝细胞凋亡，实时荧光定量PCR和Western blot检测肝组织Sirt1、乙酰化p53、Bax表达水平。

结果

RES能够显著降低由HIRI引起的ALT活力升高(

＜0.01) 并增加SOD活性(

＜0.01)，显著缓解由HIRI引起的肝脏病理学改变(

＜0.01) 和减少肝细胞凋亡(

＜0.01)，显著提高Sirt1和Bax mRNA表达水平(

＜0.01，

＜0.01)，提高Sirt1和Bax蛋白表达水平(

＜0.01，

＜0.01) 并降低乙酰化p53蛋白表达水平(

＜0.01)。

结论

RES能减轻缺血再灌注诱导的肝脏损伤，该保护作用部分是通过激动Sirt1-p53通路实现。

Abstract

Objective

To investigate the effect of resveratrol (RES) on hepatic ischemia reperfusion injury (HIRI) in rats and explore the underlying molecular mechanism.

Methods

Twenty male SD rats (aged 6 weeks

weighting

200±20 g) were randomly divided into 4 groups (

=5): sham operation group

HIRI group

RES pretreatment group

and RES pretreatment + inhibitor group. The rat model of 70% hot liver ischemia-reperfusion was established through ischemia for 1 h followed by reperfusion for 6 h. RES and Sirt1 inhibitors

EX527 were gave in the rats from the pretreatment group 1 h before the model infliction. Serum ALT activity and SOD activity in liver tissue were detected. The pathological changes of liver tissues were observed by HE staining. The apoptosis of hepatocytes were detected by TUNEL. The expression levels of Sirt1

acetylation p53 and Bax were analyzed by real-time fluorescent quantitative PCR and Western blotting.

Results

RES significantly reduced the increased ALT activity caused by HIRI (

0.01) and enhanced the activity of SOD (

0.01)

alleviated the pathological changes of the liver tissues induced by HIRI (

0.01)

and decreased the apoptosis of liver cells (

0.01). Moreover

RES obviously increased of the transcriptional levels of Sirt1 and Bax (

0.01)

improved their protein levels (

0.01)

but down-regulated the expression of acetylation p53 at protein level (

0.01).

Conclusion

RES attenuates the liver injury induced by ischemia reperfusion

which may be partially through activation of Sirt1-p53 signaling pathway.

关键词

Keywords

references

KAPAN M, GUMUS M, ONDER A, et al . The effects of ellagic acid on the liver and remote organs' oxidative stress and structure after hepatic ischemia reperfusion injury caused by pringle maneuver in rats[J ] . Bratisl Lek Listy, 2012, 113(5): 274-281. DOI:10.4149/bll_2012_064.

Gonul Y, Kazandı S, Kocak A, et al . Interleukin-18 binding protein pretreatment attenuates kidney injury induced by hepatic ischemia reperfusion[J ] . AmJMed Sci, 2016, 352(2): 200-207. DOI:10.1016/j.amjms.2016.04.012.

YOUNISNN, SHAHEENMA, MAHMOUDMF. Silymarin preconditioning protected insulin resistant rats from liver ischemia-reperfusion injury: role of endogenous H2S[J]. JSurg Res, 2016, 204(2): 398-409. DOI:10.1016/j.jss.2016.04.069.

GUANLY. Mechanisms of hepatic ischemia-reperfusion injury and protective effects of nitric oxide[J]. World Journal of Gastrointestinal Surgery, 2014, 6(7): 122. DOI:10.4240/wjgs.v6.i7.122.

HU Y, TAO X, HAN X, et al . Dioscin attenuates gastric ischemia/reperfusion injury through the down-regulation of PKC/ERK1/2 signaling via PKCα and PKCβ2 inhibition[J ] . Chem Biol Interact, 2016, 258: 234-244. DOI:10.1016/j.cbi.2016.09.014.

SASCA D, HHNELPS, KHAWAJA K, et al . SIRT1 prevents genotoxicstress-induced p53 activation in acute myeloid leukemia[J ] . Blood, 2014, 124(1) : 121-133.DOI: 10.1182/blood-2013-11-538819.

LIU L, WANG P, LIU X, et al . Exogenous NAD(+) supplementation protects H9c2 cardiac myoblasts against hypoxia/reoxygenation injury via Sirt1-p53 pathway[J ] . Fundam Clin Pharmacol, 2014, 28(2): 180-189. DOI:10.1111/fcp.12016.

LisachevPD, PustylnyakVO, ShtarkMB. Sirt1 regulates p53 stability and expression of its target S100B during long-term potentiation in rat hippocampus[J]. Bull Exp Biol Med, 2016, 160(4): 432-434. DOI:10.1007/s10517-016-3189-5.

安梅, 周瑾, 陈晓宇.白藜芦醇药理学作用的研究进展[J].肿瘤药学, 2014, 4(4): 242-246. DOI:10.3969/j.issn.2095-1264.2014.049.

AN M, ZHOU J, ChenXY. Pharmacological activities of resveratrol and protection research[J]. Anti-Tumor Pharm, 2014, 4(4) : 242-246.DOI:10.3969/j.issn.2095-1264.2014.049

THOMPSONAM, MARTINKA, RZUCIDLOEM. Resveratrol induces vascular smooth muscle cell differentiation through stimulation of SirT1 and AMPK[J]. PLoS ONE, 2014, 9(1): e85495. DOI:10.1371/journal.pone.0085495.

PANGENI R, SAHNI JK, ALI J, et al . Resveratrol: review on therapeutic potential and recent advances in drug delivery[J ] . Expert Opin Drug Deliv, 2014, 11(8): 1285-1298. DOI:10.1517/17425247.2014.919253.

ZHANG T, SHUHH, CHANG L, et al . Resolvin D1 protects against hepatic ischemia/reperfusion injury in rats[J ] . Int Immunopharmacol, 2015, 28(1): 322-327. DOI:10.1016/j.intimp.2015.06.017.

ANDERSONCD, PIERCE J, NICOUD I, et al . Modulation of mitochondrial calcium management attenuates hepatic warm ischemia-reperfusion injury[J ] . Liver Transplantation, 2005, 11(6): 663-668. DOI:10.1002/lt.20407.

ZHANG C, FENG Y, QU S, et al . Resveratrol attenuates doxorubicin-induced cardiomyocyte apoptosis in mice through SIRT1-mediated deacetylation of p53[J ] . Cardiovasc Res, 2011, 90(3): 538-545. DOI:10.1093/cvr/cvr022.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Resveratrol promotes hepatic lipid decomposition by regulating ATGL/CGI58 and Rab7/LC3β through perilipin 2

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

Resveratrol promotes axonal regeneration via PI3K/Akt pathway in rats after intracerebral hemorrhage

Resveratrol protects human umbilical vein endothelial cells against oxidative injury by activating transcription factor EB in vitro

Resveratrol improves lipid droplets lipolysis via up-regulating PKA-PLIN2 pathway in HepG2 cells

Related Author

杨依林

张艳

秦玉

糜漫天

李方

曹建民

翟鹏飞

王建设

Related Institution

Center of Nutrition and Food Safety, Chongqing Center of Medical Nutrition, Chongqing Key Laboratory of Nutrition and Food Safety, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University)

Department for Nutrition and Food Safety, Chongqing Center of Medical Nutrition, Chongqing Key Laboratory of Nutrition and Food Safety, College of Military Preventive Medicine, Third Military Medical University

Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Center of Medical Nutrition, College of Military Preventive Medicine, Third Military Medical University

Chongqing Key Laboratory of Psychological Diagnosis and Educational Technology for Children with Special Needs, College of Education Science, Chongqing Normal University

Faculty of Education for Children with Special Needs, College of Education Science, Chongqing Normal University

⁰