乔松素对对乙酰氨基酚诱发的肝损伤小鼠模型的保护作用

杜毅超; 张浩; 仲富瑞; 程宦立; 赖莉; 钱保林; 谭鹏; 夏先明; 付文广

doi:10.3969/j.issn.1001-5256.2020.03.027

乔松素对对乙酰氨基酚诱发的肝损伤小鼠模型的保护作用

DOI: 10.3969/j.issn.1001-5256.2020.03.027

1. 西南医科大学附属医院四川省院士(专家)工作站
2. 西南医科大学附属医院肝胆外科

基金项目:

四川省应用基础研究基金(2018JY0283)；四川省定向财力转移支付科技项目(2017SZYZF0015)；

详细信息

中图分类号: R285.5;R-332
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出版历程
- 收稿日期: 2019-12-12
- 出版日期: 2020-03-20

Protective effect of pinocembrin in a mouse model of liver injury induced by acetaminophen

Academician ( Expert) Workstation of Sichuan Province,Department of Hepatobiliary Surgery,The Affiliated Hospital of Southwest Medical University

Research funding:

摘要

摘要: 目的探索乔松素（PIN）对对乙酰氨基酚（APAP）诱发肝损伤小鼠模型的保护作用。方法 50只健康雄性C57BL/6J小鼠随机分成空白组、PIN（50 mg/kg）组、APAP（300 mg/kg）模型组、PIN（30 mg/kg）+APAP（300 mg/kg）组和PIN（50 mg/kg）+APAP（300 mg/kg）实验组,每组各10只。各组采取灌胃给药,空白对照组和模型组给予等量的生理盐水,PIN组及PIN+APAP组每日给药1次,连续给药7 d。末次给药2 h后,模型组和PIN+APAP组腹腔注射APAP 300 mg/kg 1次,空白组和PIN组腹腔注射等量生理盐水。收集血清,检测ALT、AST水平,肝组织匀浆检测丙二醛（MDA）、超氧化物歧化酶（SOD）及谷胱甘肽（GSH）生化指标,HE染色观察肝脏组织病理情况。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果与空白组比校,APAP（300 mg/kg）模型组的ALT、AST水平显著升高（P <0. 01）,模型构建成功; PIN（30 mg/kg）+APAP（300 mg/kg）及PIN...
- 药物性肝损伤 /
- 对乙酰氨基酚 /
- 乔松素 /
- 小鼠,近交C57BL /
- 疾病模型,动物
Abstract: Objective To investigate the protective effect of pinocembrin( PIN) in a mouse model of liver injury induced by acetaminophen( APAP). Methods A total of 50 healthy male C57BL/6 J mice were randomly divided into blank group,PIN( 50 mg/kg) group,APAP( 300 mg/kg) model group,PIN( 30 mg/kg) + APAP( 300 mg/kg) experimental group,and PIN( 50 mg/kg) + APAP( 300 mg/kg) experimental group,with 10 mice in each group. The mice in the blank group and the model group were given an equal volume of normal saline by gavage,and those in the PIN group and the PIN + APAP groups were given PIN by gavage once a day,for 7 consecutive days. At 2 hours after the last administration,the mice in the model group and the PIN + APAP groups were given intraperitoneal injection of APAP 300 mg/kg once,and those in the blank group and the PIN group were given intraperitoneal injection of an equal volume of normal saline. Serum samples were collected to measure the levels of alanine aminotransferase( ALT) and aspartate aminotransferase( AST); liver tissue homogenate was prepared to measure the biochemical parameters of malondialdehyde( MDA),superoxide dismutase( SOD),and glutathione( GSH);HE staining was used to observe liver histopathology. A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups. Results Compared with the blank group,the APAP( 300 mg/kg) model group had significant increases in the activities of ALT and AST( P < 0. 01),suggesting that a model was successfully established,while the PIN( 30 mg/kg) + APAP( 300 mg/kg) group and the PIN( 50 mg/kg) + APAP( 300 mg/kg) group had significant reductions in the levels of ALT and AST( P < 0. 01). Compared with the blank group,the APAP( 300 mg/kg)model group had a significant increase in the level of MDA and significant reductions in SOD activity and GSH level in the liver( P < 0. 01);compared with the APAP( 300 mg/kg) model group,the PIN( 30 mg/kg) + APAP( 300 mg/kg) group and the PIN( 50 mg/kg) + APAP( 300 mg/kg) group had a significant reduction in the level of MDA and significant increases in SOD activity and GSH level in the liver( P <0. 05). Histopathological observation showed that PIN significantly improved liver injury caused by APAP and helped to maintain normal liver histomorphology. Conclusion PIN exerts a marked protective effect on liver injury induced by APAP,possibly by inhibiting oxidative stress in the liver.
- drug-induced liver injury /
- acetaminophen /
- pinocembrin /
- mice,inbred C57BL /
- disease models,animal

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参考文献(17)

[1] VUPPALANCHI R,LIANGPUNSAKUL S,CHALASANI N. Etiology of new-onset jaundice:How often is it caused by idiosyncratic drug-induced liver injury in the United States?[J].Am J Gastroenterol,2007,102(3):558-562; quiz 693.

[2] CHAYANUPATKUL M,SCHIANO TD. Acute liver failure secondary to drug-induced liver injury[J]. Clin Liver Dis,2020,24(1):75-87.

[3] JAESCHKE H,MCGILL MR,RAMACHANDRAN A. Oxidant stress,mitochondria,and cell death mechanisms in drug-induced liver injury:Lessons learned from acetaminophen hepatotoxicity[J]. Drug Metab Rev,2012,44(1):88-106.

[4] ZHANG TT,XU XL,JIANG MH,et al. Hepatoprotective function of Penthorum Chinense Pursh[J]. Food Funct,2013,4(11):1581-1585.

[5] ZHANG X,MENG CW,HE YC,et al. Study on Flavonoids of Penthorum Chinense[J]. Chin Tradit Herb Drug,2017,48(1):31-35.(in Chinese)张潇，蒙春旺，何亚聪，等．赶黄草黄酮类化学成分研究[J]．中草药，2017,48(1):31-35.

[6] ZHOU F,WANG A,LI D,et al. Pinocembrin from Penthorum chinense Pursh suppresses hepatic stellate cells activation through a unified SIRT3-TGF-β-Smad signaling pathway[J]. Toxicol Appl Pharmacol,2018,341:38-50.

[7] ZHANG HW,ZHANG L. Research progress on pinocembrin:Potential therapeutic applications and action mechanisms[J]. Acta Neuropharmacologica,2016,6(5):45-52.(in Chinese)张海威，张力．乔松素临床应用和作用机制的研究进展[J]．神经药理学报，2016,6(5):45-52.

[8] QI J,ZHOU Z,LIM CW,et al. Amlexanox ameliorates acetaminophen-induced acute liver injury by reducing oxidative stress in mice[J]. Toxicol Appl Pharmacol,2019,385:114767.

[9] YOON E,BABAR A,CHOUDHARY M,et al. Acetaminophen-induced hepatotoxicity:A comprehensive update[J]. J Clin Transl Hepatol,2016,4(2):131-142.

[10] YAN M,HUO Y,YIN S,et al. Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions[J]. Redox Biol,2018,17:274-283.

[11] JIANG H,BAI XF. Research advances in acute liver failure[J]. J Clin Hepatol,2018,34(9):1824-1831.(in Chinese)姜泓，白雪帆．急性肝衰竭研究进展[J]．临床肝胆病杂志，2018,34(9):1824-1831.

[12] YU PF,WU Q,DUAN ZP,et al. Research advances in the mechanism of drug-induced liver injury due to paracetamol[J]. J Clin Hepatol,2019,35(9):2108-2112.(in Chinese)余朋飞，吴桥，段钟平，等．对乙酰氨基酚致药物性肝损伤的机制研究进展[J]．临床肝胆病杂志，2019,35(9):2108-2112.

[13] KON K,KIM JS,JAESCHKE H,et al. Mitochondrial permeability transition in acetaminophen-induced necrosis and apoptosis of cultured mouse hepatocytes[J]. Hepatology,2004,40(5):1170-1179.

[14] SAAD MA,ABDEL SALAM RM,KENAWY SA,et al. Pinocembrin attenuates hippocampal inflammation,oxidative perturbations and apoptosis in a rat model of global cerebral ischemia reperfusion[J]. Pharmacol Rep,2015,67(1):115-122.

[15] PROMSAN S,JAIKUMKAO K,PONGCHAIDECHA A,et al.Pinocembrin attenuates gentamicin-induced nephrotoxicity in rats[J]. Can J Physiol Pharmacol,2016,94(8):808-818.

[16] FAN L,XIE XX,CHEN L,et al. Protective effects of three Penthorum Chinense extracts on endotoxin-induced liver injury in mice[J]. Chin Tradit Patent Med,2019,41(2):291-297.(in Chinese)范玲，谢星星，陈立，等．赶黄草3种提取物对小鼠内毒素性肝损伤的保护作用[J]．中成药，2019,41(2):291-297.

[17] PUNVITTAYAGUL C,WONGPOOMCHAI R,TAYA S,et al.Effect of pinocembrin isolated from Boesenbergia pandurata on xenobiotic-metabolizing enzymes in rat liver[J]. Drug Metab Lett,2011,5(1):1-5.

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