[1]李悦宁,肖柯心,赵冰洁,等.桑玉膏对对乙酰氨基酚诱导的小鼠急性肝损伤保护作用研究[J].陕西中医,2023,(2):154-158.[doi:DOI:10.3969/j.issn.1000-7369.2023.02.004]
 LI Yuening,XIAO Kexin,ZHAO Bingjie,et al.Protective effects of Sangyu ointment against acetaminophen-induced acute liver failure in mice[J].,2023,(2):154-158.[doi:DOI:10.3969/j.issn.1000-7369.2023.02.004]
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桑玉膏对对乙酰氨基酚诱导的小鼠急性肝损伤保护作用研究
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2023年2期
页码:
154-158
栏目:
基础研究
出版日期:
2023-02-05

文章信息/Info

Title:
Protective effects of Sangyu ointment against acetaminophen-induced acute liver failure in mice
作者:
李悦宁12肖柯心23赵冰洁23李红玉23王 番2詹 博23贾艳艳12
(1.西北大学生命科学学院,陕西 西安 710069; 2.空军军医大学第一附属医院药剂科,陕西 西安 710032; 3.陕西中医药大学药学院,陕西 咸阳 712046)
Author(s):
LI YueningXIAO KexinZHAO BingjieLI HongyuWANG FanZHAN BoJIA Yanyan
(College of Life Sciences,Northwestern University,Xi'an 710069,China)
关键词:
药物性肝损伤 桑玉膏 对乙酰氨基酚 炎症因子 氧化应激 保护作用
Keywords:
Drug-induced liver injury Sangyu ointment Acetaminophen Inflammatory factors Oxidative stress Protective effects
分类号:
R 965.1
DOI:
DOI:10.3969/j.issn.1000-7369.2023.02.004
文献标志码:
A
摘要:
目的:探究桑玉膏对对乙酰氨基酚(APAP)诱导的小鼠肝损伤的保护作用及其作用机制。方法:将60只雄性健康昆明种小鼠随机分成空白对照组,APAP模型组,N-乙酰半胱氨酸(NAC)阳性药物组,桑玉膏低、中、高剂量组,除空白对照组外其他各组腹腔注射APAP,建立药物性肝损伤(DILI)小鼠模型,灌胃给药5 d后,腹腔主动脉取血,收集肝脏组织。生化法检测血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、碱性磷酸酶(ALP)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、一氧化氮(NO)活性水平或含量,酶联免疫吸附测定法(ELISA)检测肝组织中肿瘤坏死因子-α(TNF-α)、重组人白细胞介素-1β(IL-1β)含量,实时定量PCR法(qRT-PCR)检测肝脏组织中促凋亡蛋白Bax和抑凋亡蛋白Bcl-2的mRNA表达。结果:与APAP模型组比较,桑玉膏各剂量组小鼠ALT、AST、ALP 水平显著降低(P<0.01),肝组织损伤、炎性细胞浸润明显减轻; SOD、GSH-PX活性升高(P<0.01),TNF-α、IL-1β、MDA及NO活性或含量下降(P<0.01),肝脏组织中促凋亡蛋白Bax的mRNA表达显著下降,抑凋亡蛋白Bcl-2的mRNA表达显著升高(P<0.01)。结论:桑玉膏对APAP诱导的小鼠药物性肝损伤有保护作用,其作用机制可能与提高机体抗氧化能力、缓解氧化应激、降低炎症因子水平等有关。
Abstract:
Objective:To investigate the protective effects and mechanism of Sangyu ointment on acute liver failure induced by acetaminophen(APAP)in mice.Methods:Sixty healthy male kunming mice,were randomly divided into blank control group,APAP model group,N-acetylcysteine(NAC)positive drug group and low-dose,middle-dose and high-dose of Sangyu ointment groups.The mice model of drug-induced liver injury was established by intraperitoneal injection of APAP in all groups except blank control group.The blood was collected from abdominal aorta and liver tissue was collected after the mice were given therapeutic intragastric administration for 5 days.The activities of AST,ALT,ALP,MDA,SOD,GSH-PX and NO in serum were detected by biochemical analysis,the contents of TNF-α and IL-1β in liver tissue were detected by ELISA and the mRNA expression of pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2 in liver tissue was detected by qRT-PCR.Results:Compared with APAP model group,the activities of ALT,AST and ALP in the three groups of Sangyu ointment were significantly decreased(P<0.01),liver tissue injury and inflammatory cell infiltration were reduced,and the activities of SOD and GSH-PX were increased(P<0.01).Meanwhile,the contents of TNF-α,IL-1β,MDA and NO decreased in the Sangyu ointment groups(P<0.01).Finally,compared with APAP model group,the mRNA expression of pro-apoptotic protein Bax in liver tissue was decreased,and the mRNA expression of anti-apoptotic protein Bcl-2 was significantly increased in the three groups of Sangyu ointment(P<0.01).Conclusion:Sangyu ointment has a protective effect on drug-induced liver injury induced by APAP in mice,and its mechanism may be related to improving antioxidant capacity,alleviating oxidative stress and reducing the level of inflammatory factors.

参考文献/References:

[1] Li XY,Tang JT,Mao YM.Incidence and risk factors of drug-induced liver injury[J].Liver Int,2022,42(9):1999-2014.
[2] Yonezuka Y,Kuwada H,Imaishi H.Diagnosis of drug-induced liver injury in model mice by studying the inhibitory effect of serum components on P450 inhibition assay[J].Chem Biol Interact,2022,365:110075.
[3] Heldring MM,Shaw AH,Beltman JB.Unraveling the effect of intra- and intercellular processes on acetaminophen-induced liver injury[J].NPJ Syst Biol Appl,2022,8:27.
[4] Moreno TM,Quintás G,Castell JV.The potential role of metabolomics in drug-induced liver injury(DILI)assessment[J].Metabolites,2022,12(6):564.
[5] Shen T,Liu YX,Shang J,et al.Incidence and etiology of drug-induced liver injury in mainland China[J].Gastroenterology,2019,156:2230-2241.
[6] Long A,Magrath M,Mihalopoulos M,et al.Changes in epidemiology of acetaminophen overdoses in an urban county hospital after 20 years[J].Am J Gastroenterol,2022,117:1324-1328.
[7] 刘应莉,王艳荣,张秋瓒.肠道菌群-过氧化物酶体增殖物激活受体信号通路及其在代谢相关脂肪性肝病发病中的作用研究进展[J].陕西医学杂志,2021,50(9):1166-1168.
[8] 胡锦华,娄月芬.药物性肝损伤发病机制与诊疗的研究进展[J].上海医学,2020,43(11):699-704.
[9] Li M,Luo Q,Tao YY,et al.Pharmacotherapies for drug-induced liver injury:A current literature review[J].Front Pharmacol,2021,12:806249.
[10] Licata A,Minissale M,Giovanna,SS,et al.N-acetylcysteine for preventing acetaminophen-induced liver injury:A comprehensive review[J].Front Pharmacol,2022,13:828565.
[11] Peng Y,Zhu GR,Ma YY,et al.Network pharmacology-based prediction and pharmacological validation of effects of astragali radix on acetaminophen-induced liver injury[J].Front Med(Lausanne),2022,9:697644.
[12] 陈俐秀,蒋璐慧,卢顺玉,等.柿寄生提取物对对乙酰氨基酚诱导小鼠肝损伤的保护作用及作用机制[J].中国医院药学杂志,2019,39(14):1435-1438.
[13] 艾丁丁,罗伟生,蒋云霞.动物肝纤维化模型建立研究进展[J].陕西医学杂志,2020,49(7):907-909.
[14] 吴佳栩,江 锋,薛 婧.中医药治疗药物性肝损伤的现状与思考[J].中西医结合肝病杂志,2021,31(12):1119-1122.
[15] 黄祖鸿,石清兰,柏文婕,等.毛德文教授运用“调肝理脾”法治疗慢性肝病经验总结[J].陕西中医,2021,42(8):1112-1114,1119.
[16] 雷 玲,闵 珺,刘 锋,等.黄芪对肝纤维化大鼠肝损伤保护作用及机制研究[J].陕西中医,2020,41(9):1192-1196.
[17] Bjornsson ES,Vucic V,Stirnimann G,et al.Role of corticosteroids in drug-induced liver injury:A systematic review[J].Front Pharmacol,2022,13:820724.
[18] Jiang XL,Luo PY,Zhou YY,et al.Oplopanax elatus hepatoprotective effect of nakai adventitious roots extract by regulating CYP450 and PPAR signaling pathway[J].Front Pharmacol,2022,13:761618.
[19] Wang L,Zhang LY,Wang JY,et al.Protective effect of dandelion leaf water extracts on APAP-induced liver injury in rats and its mechanism[J].Cell Mol Biol(Noisy-le-grand),2022,68:24-33.
[20] Guo HT,Xie MJ,Liu WX,et al.Inhibition of BTK improved APAP-induced liver injury via suppressing proinflammatory macrophages activation by restoring mitochondrion function[J].Int Immunopharmacol,2022,110:109036.
[21] Jiang ZT,Yang X,Han Y,et al.Sarmentosin promotes USP17 and regulates Nrf2-mediated mitophagy and cellular oxidative stress to alleviate APAP-induced acute liver failure[J].Phytomedicine,2022,104:154337.
[22] Wang JC,Zhang LL,Shi Q,et al.Targeting innate immune responses to attenuate acetaminophen-induced hepatotoxicity[J].Biochem Pharmacol,2022,202:115142.
[23] 唐文诚,何 清.枳椇水提物对对乙酰氨基酚致小鼠急性肝损伤的相关机制研究[J].药物分析杂志,2021,41(2):245-251.

备注/Memo

备注/Memo:
基金项目:陕西省重点研发计划项目(2020ZDLSF03-09)
更新日期/Last Update: 2023-02-08