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硫化氢预处理对扑热息痛引起肝损伤的保护作用
作者:黄海进1  施洋2  仲艳阳2  陈大六2  焦峰1 
单位:1. 江苏淮安市洪泽区人民医院 普外科, 江苏 淮安 223001;
2. 解放军第八二医院 普外科, 江苏 淮安 223001
关键词:扑热息痛 肝损伤 硫化氢 MAPK/JNK 信号途径 
分类号:R575
出版年·卷·期(页码):2018·37·第一期(1-5)
摘要:

目的:观察硫化氢对于扑热息痛引起肝损伤的保护作用及相关机制。方法:将正常雄性C57小鼠20只随机分为正常组、扑热息痛组、硫化氢预处理组以及单纯硫化氢处理组。在分别给予相应的处理后,于扑热息痛处理后8 h处死小鼠并检测各组小鼠血生化指标,观察各组小鼠肝脏组织病理学变化以及相关关键蛋白的变化。结果:扑热息痛引能够引起小鼠血清ALT、AST明显升高,光镜下小鼠肝脏呈现大面积坏死。而在硫化氢预处理后,相较于模型组前者小鼠ALT、AST的表达明显下降、肝脏损伤显著减轻。于此同时,扑热息痛损伤后,小鼠肝内凋亡相关蛋白Cleaved-Caspase3、Bax明显上调,Bcl-2的表达下降,MAPK/JNK信号通路被激活。而在H2S预处理以后,小鼠肝内Cleaved-Caspase3、Bax的表达下降、Bcl-2的表达升高。同时,MAPK/JNK信号通路的活化受到抑制。结论:H2S可以通过抑制MAPK/JNK信号途径从而减少肝细胞的损伤。

Objective: To explore the effect of H2S on liver injury caused by acetaminophen (APAP). Methods: Male C57BL/6J mice(n=20)were divided randomly into control group, APAP group, APAP+H2S group and H2S group. Eight hours they were treated with APAP, serum biochemical levels, the changes of morphological structure and the expression of related proteins were tested in all the groups. Results: After APAP treated, the level of ALT, AST were increased and massive necrosis could be observed under the pathologic microscope. Compared with APAP group, mice had lower ALT and AST, shown less tissue necrosis after H2S treatment. Meanwhile, APAP increased the expression of apoptotic proteins Cleaved-Caspase3 and Bax, inhibited the expression of Bcl-2 and activated MAPK/JNK signaling pathway. After H2S treatment, the expression of Cleaved-Caspase3 and Bax were reduced, Bcl-2 was increased and MAPK/JNK signaling pathway was supreessed. Conclusion: H2S can attenuate the APAP induced liver damage by inhibiting MAPK/JNK signaling pathway.

参考文献:

[1] OSTAPOWICZ G,FONTANA R J,SCHIØDT F V,et al.Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States[J].Ann Intern Med,2002,137(12):947-54.
[2] GUNAWAN B K,LIU Z X,HAN D,et.al.c-Jun N-terminal kinase plays a major role in murine acetaminophen hepatotoxicity[J].Gastroenterology,2006,131(1):165-78.
[3] LIU F C,LEE H C,LIAO C C,et.al.Tropisetron protects against acetaminophen-induced liver injury via suppressing hepatic oxidative stress and modulating the activation of jnk/erk mapk pathways[J].Biomed Res Int,2016(1):1952947
[4] 唐小卿,杨春涛,冯鉴强.第三种气体信号分子硫化氢的神经保护作用研究进展[J].中南医学科学杂志,2012,40(1):1-5.
[5] 兰爱平,梅卫义,孟金兰,等.硫化氢通过抑制p38 MAPK保护PC12细胞对抗化学性缺氧损伤[J].中国药理学通报,2010,26(10):1339-1344.
[6] 于水,杨海扣,米琰,等.PI3K/Akt信号通路在外源性硫化氢后处理大鼠离体心肌中的作用[J].中国药理学通报,2010,26(6):759-764.
[7] ZHOU X,ZHAO L,MAO J,et.al.Antioxidant effects of hydrogen sulfide on left ventricular remodeling in smoking rats are mediated via PI3K/Akt-dependent activation of Nrf2[J].Toxicol Sci,2015,144(1):197-203.
[8] SAKAMOTO K,SUZUKI Y,KURAUCHI Y,et al.Hydrogen sulfide attenuates NMDA-induced neuronal injury via its anti-oxidative activity in the rat retina[J].Exp Eye Res,2014,120:90-96.
[9] 张昱,程卫平.硫化氢对乳鼠心肌细胞缺氧-复氧损伤的保护作用[J].中国循环杂志,2009,24(3):227-230.
[10] 陈军宝,徐智,覃小艳,等.扑热息痛肝损伤机制的研究进展[J].实用医学杂志,2012,28(20):3479-3480.
[11] TASLIPINAR M Y,AYDIN I,KALDIRIM U,et al.Hyperbaric oxygen treatment and N-acetylcysteine ameliorate acetaminophen-induced liver injury in a rat model[J].Hum Exp Toxicol,2013,32(10):1107-16.
[12] I·ÇER M,ZENGIN Y,GUNDUZ E,et al.Is montelukast as effective as N-acetylcysteine in hepatic injury due to acetaminophen intoxication in rats[J].Exp Toxicol Pathol,2016,68(1):55-59.
[13] WANG R.Two's company,three's a crowd:can H2S be the third endogenous gaseous transmitter[J].FASEB J,2002,16(13):1792-1798.
[14] JOHANSEN D,YTREHUS K,BAXTER GF.Exogenous hydrogen sulfide (H2S) protects against regional myocardial ischemia-reperfusion injury——Evidence for a role of K ATP channels[J].Basic Res Cardiol,2006,101(1):53-60.
[15] 覃志成,刘文丽,李光远,等.硫化氢通过抑制氧化应激减轻肾脏缺血再灌注损伤[J].中华肾脏病杂志,2016,32(2):138-142.
[16] XU W,CHEN J,LIN J,et al.Exogenous H2S protects H9c2 cardiac cells against high glucose-induced injury and inflammation by inhibiting the activation of the NF-κB and IL-1β pathways[J].Int J Mol Med,2015,35(1):177-186.
[17] LIU M H,LIN X L,ZHANG Y,et al.Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibiting reactive oxygen species-activated extracellular signal-regulated kinase 1/2 in H9c2 cardiac myocytes[J].Mol Med Rep,2015,12(5):6841-6848.

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