您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (1): 10-15.doi: 10.6040/j.issn.1671-7554.0.2014.715

• 基础医学 • 上一篇    下一篇

口服富氢水对小鼠脂肪肝缺血再灌注损伤的保护作用

李少伟1,2, 刘宗正1,2, 刘春霞1,2, 张焱如1,2, 周欢敏1,2   

  1. 1. 内蒙古农业大学生命科学学院, 内蒙古 呼和浩特 010018;
    2. 内蒙古自治区生物制造重点实验室, 内蒙古 呼和浩特 010018
  • 收稿日期:2014-10-16 修回日期:2014-12-17 发布日期:2015-01-10
  • 通讯作者: 周欢敏。E-mail:huanminzhou@263.net E-mail:huanminzhou@263.net
  • 基金资助:
    内蒙古自然科学基金重大项目(2010ZD10)

Hydrogen-rich water alleviates ischemia-reperfusion injury in mice with fatty liver

LI Shaowei1,2, LIU Zongzheng1,2, LIU Chunxia1,2, ZHANG Yanru1,2, ZHOU Huanmin1,2   

  1. 1. College of Life Sciences, Inner Mongolia Agricultural University, Hohhot 010018, Inner Mongolia, China;
    2. Inner Mongolia Key Laboratory of Biomanufacture, Hohhot 010018, Inner Mongolia, China
  • Received:2014-10-16 Revised:2014-12-17 Published:2015-01-10

PDF (PC)

200

摘要： 目的 探讨富氢水对脂肪肝缺血再灌注损伤小鼠模型的保护作用。方法 将30只C57BL/6小鼠随机分为3组。假手术组:喂蛋氨酸胆碱缺乏高脂饮食非酒精性脂肪肝造模;对照组:肝脏缺血再灌注前灌服蒸馏水;富氢水缺血再灌注组:肝脏缺血再灌注前灌服富氢水,再灌注6 h后处死小鼠,检测血清中AST和ALT含量,观察肝脏组织形态学变化,分析肝脏组织损伤程度、巨噬细胞浸润、炎性因子TNF-α、IL-6、 OPN mRNA表达水平和肝脏组织内活化的Caspase-3蛋白表达水平。结果 与对照组相比较,富氢水组血清ALT和AST水平较低(P<0.05),巨噬细胞浸润和凋亡细胞明显减少,炎性因子mRNA的表达明显降低。Caspase-3表达明显降低。结论 富氢水能够减轻脂肪肝小鼠肝脏缺血再灌注损伤,其机制与富氢水抑制氧化应激反应和炎症反应,进而抑制Caspase-3蛋白表达有关。

关键词: 富氢水, 缺血再灌注损伤, 氧化应激, 非酒精性脂肪肝, 炎症反应

Abstract: Objective To explore the protective effect of hydrogen-rich water on liver ischemia-reperfusion (I/R) in mice models with fatty liver and the possible mechanism. Methods A total of 30 C57BL/6 mice were randomly divided into 3 groups: sham-operated group (SO), control group (mice with steatotic liver perfused with water before ischemia induction) and hydrogen-rich water group (mice with steatotic liver perfused with hydrogen-rich water before ischemia reperfusion). Six hours after reperfusion, the mice were sacrificed, and serum and liver samples were collected. The ALT and AST levels in serum were determined and liver histological damage was evaluated. The infiltration of macrophages was detected. The mRNA expressions of TNF-α, IL-6, and OPN mRNA were assayed using real-time reverse transcription PCR. The expression of activated Caspase-3 was checked with Western blotting. Results Compared with control group, 6 hours following reperfusion, mice in hydrogen-rich water group exhibited lower levels of ALT and AST (P<0.05), lower expression of inflammatory cytokines and Caspase-3, milder histological damage, and less infiltration of macrophages (P<0.05). Conclusion Hydrogen-rich water given by gavage can alleviate steatotic liver ischemia-reperfusion injury by inhibiting oxidant stress, inflammatory response and apoptosis induced by reperfusion.

Key words: Nonalcoholic fatty liver, Hydrogen rich water, Reperfusion injury, Oxidant stress, Inflammatory

中图分类号: 

  • R575
[1] Bhala N, Angulo P, van der Poorten D, et al. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study[J]. Hepatology, 2011, 54(4):1208-1216.
[2] Bhala N, Usherwood T, George J. Non-alcoholic fatty liver disease [J]. BMJ, 2009, 339: b2474. doi: 10.1136/bmj.b2474.
[3] Yang YY, Lee PC, Huang YT, et al. Involvement of the HIF-1alpha and Wnt/beta-catenin pathways in the protective effects of losartan on fatty liver graft with ischaemia/reperfusion injury[J]. Clin Sci (Lond), 2014, 126(2):163-174.
[4] Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals[J]. Nat Med, 2007, 13(6):688-694.
[5] Sun H, Chen L, Zhou W, et al. The protective role of hydrogen-rich saline in experimental liver injury in mice[J]. J Hepatol, 2011, 54(3):471-480.
[6] Theruvath TP, Ramshesh VK, Zhong Z, et al. Icam-1 upregulation in ethanol-induced Fatty murine livers promotes injury and sinusoidal leukocyte adherence after transplantation[J]. HPB Surg, 2012, 2012:480893. doi:10.1155/2012/480893.
[7] 游玉霞, 李建军, 李玉洁, 等. 富氢水对大鼠视神经夹伤模型视网膜神经节细胞保护作用的实验研究[J]. 眼科, 2014, 23(2):107-110. YOU Yuxia, LI Jianjun, LI Yujie, et al. Neuroprotective effects of saturated hydrogen water on retinal ganglion cells in rat optic nerve crush model[J]. Ophthalmol CHN, 2014, 23(2):107-110.
[8] 曾葵, 黄瀚, 江晓琴, 等. 氢气对大鼠肾脏缺血再灌注损伤的保护作用[J]. 四川大学学报:医学版, 2014, 45(1):39-42. ZENG Kui, HUANG Han, JIANG Xiaoqin, et al. Protective Effects of Hydrogen on renal Ischemia/Reperfusion Injury in Rat[J]. J Sichuan Univ: Med Sci Edi, 2014, 45(1):39-42.
[9] 刘琪, 王大为, 陈兴, 等. 氢气对吸入性损伤大鼠急性肺损伤的保护作用及量效研究[J].天津医科大学学报, 2013, 19(6):445-448. LIU Qi, WANG Dawei, CHEN Xing, et al. Protective effects of hydrogen gas on acute lung injury induced by smoke inhalation in rats and its dose effect relationship[J]. Journal of Tianjin Medical University, 2013, 19(6):445-448.
[10] Kudo H, Yata Y, Takahara T, et al. Telmisartan attenuates progression of steatohepatitis in mice: role of hepatic macrophage infiltration and effects on adipose tissue[J]. Liver Int, 2009, 29(7):988-996.
[11] Teramoto K, Bowers J, Kruskal JB, et al. Hepatic microcirculatory changes after reperfusion in fatty and normal liver-transplantation in the rat[J].Transplantation, 1993, 56(5):1076-1082.
[12] Diehl AM. Nonalcoholic steatosis and steatohepatitis-IV. Nonalcoholic fatty liver disease abnormalities in macrophage function and cytokines[J]. Am J Physiol Gastrointest Liver Physiol, 2002, 282(1):G1-G5.
[13] Zhang ZX, Shek K, Wang SA, et al. Osteopontin expressed in tubular epithelial cells regulates NK cell-mediated kidney ischemia reperfusion injury[J]. J Immunol, 2010, 185(2):967-973.
[14] Jiang M, Li J, Peng Q, et al. Neuroprotective effects of bilobalide on cerebral ischemia and reperfusion injury are associated with inhibition of pro-inflammatory mediator production and down-regulation of JNK1/2 and p38 MAPK activation[J]. J Neuroinflammation, 2014, 11(1):167.
[15] Liu X, Mei Z, Qian J, et al. Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway[J]. Neural Regen Res, 2013, 8(34):3203-3215.
[16] Canbay A, Feldstein AE, Higuchi H, et al. Kupffer cell engulfment of apoptotic bodies stimulates death ligand and cytokine expression[J]. Hepatology, 2003, 38(5):1188-1198.
[17] Nace GW, Huang H, Klune JR, et al. Cellular-specific role of toll-like receptor 4 in hepatic ischemia-reperfusion injury in mice[J]. Hepatology, 2013, 58(1):374-387.
[18] Qiu Z, Zhou D, Sun D. Effects of human umbilical cord mesenchymal stem cells on renal ischaemia-reperfusion injury in rats[J]. Int Braz Urol, 2014, 40(4):553-561.
[19] Serviddio G, Bellanti F, Tamborra R, et al. Uncoupling protein-2 (UCP2) induces mitochondrial proton leak and increases susceptibility of non-alcoholic steatohepatitis (NASH) liver to ischaemia-reperfusion injury[J]. Gut, 2008, 57(7):957-965.
[20] Baskin-Bey ES, Canbay A, Bronk SF, et al. Cathepsin B inactivation attenuates hepatocyte apoptosis and liver damage in steatotic livers after cold ischemia-warm reperfusion injury [J]. Am J Physiol Gastroint Liver Physiol, 2005, 288(2):G396-G402.
[21] Kamata H, Honda S, Maeda S, et al. Reactive oxygen species promote TNF alpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases[J]. Cell, 2005, 120(5):649-661.
[1] 龙婷婷,谢明,周璐,朱俊德. Noggin蛋白对小鼠脑缺血再灌注损伤后学习和记忆能力与齿状回结构的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 15-23.
[2] 蒋正,申振伟,张光,李润滋,曹瑾,王丽,薛付忠,刘言训. 基于体检人群的非酒精性脂肪肝筛查工具的建立[J]. 山东大学学报（医学版）, 2017, 55(6): 114-118.
[3] 柳晓涓,蒋正,康凤玲,周苗,林伟强,薛付忠. 中性粒细胞计数与非酒精性脂肪肝关联性的前瞻性队列研究[J]. 山东大学学报（医学版）, 2017, 55(6): 119-123.
[4] 张栾,陈欧,栾云,朱晓波,陈元,王一彪. Gemigliptin对野百合碱诱导的肺动脉高压大鼠治疗作用及炎症因子的影响[J]. 山东大学学报（医学版）, 2017, 55(5): 19-22.
[5] 樊彦伟,严冬雪,招友. 富氢水对兔腰椎间盘退变的影响[J]. 山东大学学报（医学版）, 2017, 55(3): 38-42.
[6] 梁丽宁,钟霞,季宪飞,胡浩然,朱芳芳,陈吉彬,陈茜茜,商德亚. 尼可地尔后适应对猪心脏骤停后心脑肾缺血再灌注损伤的保护作用[J]. 山东大学学报（医学版）, 2017, 55(10): 46-51.
[7] 申振伟,季晓康,王庆莲,李洁,薛付忠,刘静. 非酒精性脂肪肝与慢性肾脏病关系的回顾性队列研究[J]. 山东大学学报（医学版）, 2016, 54(7): 43-49.
[8] 林栋,管庆波. 2型糖尿病男性患者血清睾酮水平低下对非酒精性脂肪肝的影响[J]. 山东大学学报（医学版）, 2016, 54(7): 33-37.
[9] 赵秀芹,邓春颖,李世英,张晋霞,贺永贵,余红,刘斌. 丁苯酞注射液对大鼠局灶性脑缺血再灌注损伤的神经保护作用[J]. 山东大学学报（医学版）, 2016, 54(4): 25-31.
[10] 孙鹏飞,孟晓,张凯,黎莉. 抵抗素样分子 β在动脉粥样硬化斑块稳定性中的作用[J]. 山东大学学报（医学版）, 2016, 54(3): 1-4.
[11] 李欣,王公明,王红,王岩,张立功,张乐,刘蓓,张孟元. 诱导型一氧化氮合成酶参与大鼠心脏缺血后处理延迟相的保护作用[J]. 山东大学学报（医学版）, 2016, 54(2): 16-20.
[12] 李少伟, 刘宗正, 刘春霞, 张焱如, 周欢敏. 葡萄籽原花青素对小鼠脂肪肝模型缺血再灌注造成的急性肝损伤的保护作用[J]. 山东大学学报（医学版）, 2015, 53(9): 41-46.
[13] 郭长艳, 秦雪娇, 吴晓莉, 高雪, 蔡可丽. 线粒体靶向性肽SS-31对H2O2诱导人晶状体上皮细胞凋亡的保护作用[J]. 山东大学学报（医学版）, 2015, 53(8): 23-26.
[14] 张忠霞, 马晓伟, 王彦永, 李晓丽, 王铭维. 帕金森病模型小鼠黑质纹状体系统氧化应激的增龄性改变[J]. 山东大学学报（医学版）, 2014, 52(9): 26-29.
[15] 郝凤成1,2，苏中华1,3. 自噬在ox-LDL诱导炎症反应中的保护作用[J]. 山东大学学报（医学版）, 2014, 52(4): 30-34.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发