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） ›› 2014, Vol. 52 ›› Issue (10): 29-34.doi: 10.6040/j.issn.1671-7554.0.2014.401

• 基础医学 • 上一篇    下一篇

蛋氨酸亚砜还原酶B1在糖尿病小鼠肾脏中的表达变化及其与氧化应激的关系

杨志英, 刘向春, 关广聚   

  1. 山东大学肾脏病研究所 山东大学第二医院肾内科, 山东 济南 250033
  • 收稿日期:2014-06-18 修回日期:2014-09-19 出版日期:2014-10-10 发布日期:2014-10-10
  • 通讯作者: 关广聚。E-mail：guangj@sdu.edu.cn E-mail:guangj@sdu.edu.cn
  • 基金资助:
    “十二五”国家科技支撑计划（2011BAI10B00）

Expression changes of methionine sulfoxide reductase B1 in the kidneys of instreptozocin-induced diabetic mice and its relationship with oxidative stress

YANG Zhiying, LIU Xiangchun, GUAN Guangju   

  1. Nephrology Research Institute, Shandong University;
    Nephrology Department, the Second Hospital of Shandong University, Jinan 250033, Shandong, China
  • Received:2014-06-18 Revised:2014-09-19 Online:2014-10-10 Published:2014-10-10

PDF (PC)

404

摘要： 目的 探讨链脲佐菌素（STZ）诱导的糖尿病小鼠肾组织中蛋氨酸亚砜还原酶B1（MsrB1）的表达变化及其与氧化应激的关系。方法 将10周龄雄性C57BL/6小鼠随机分为4组：正常对照组（NC组）、单侧肾切除组（UX组）、STZ组和单侧肾切除加STZ组（STZ-UX组）。模型制备后第8周末，免疫组化法检测MsrB1在肾组织中的表达和分布；实时定量PCR、Western blotting检测MsrB1 mRNA及蛋白水平的变化；通过丙二醛（MDA）、蛋白羰基（PC）和总巯基（TSH）测试盒检测氧化损伤情况。结果 MsrB1表达于小鼠肾小管上皮细胞的细胞核和细胞质。与NC组相比，STZ组和STZ-UX组MsrB1表达量和TSH含量减少（P<0.05），而MDA、PC含量增加（P<0.05），且STZ-UX组比STZ组变化更明显；UX组没有明显改变（P>0.05）。相关性分析结果显示，STZ组和STZ-UX组MsrB1蛋白表达与MDA和PC呈负相关（P<0.05），与TSH含量呈正相关（P<0.05）。结论 在STZ诱导的糖尿病小鼠肾组织中，MsrB1表达明显减少，这种变化可能参与了糖尿病肾病（DN）氧化应激的发生。

关键词: 氧化应激, 糖尿病肾病, C57BL/6小鼠, 蛋氨酸亚砜还原酶B1

Abstract: Objective To determine the expression changes of methionine sulfoxide reductase B1 (MsrB1) in the kidneys of streptozotocin (STZ)-induced diabetic mice and to investigate its relationship with oxidative stress. Methods Ten-week-old male C57BL/6 mice were randomly divided into four groups: normal control mice group (NC group), unilaterally nephrectomized mice group (UX group), STZ-induced diabetic mice group (STZ group) and STZ mice with unilateral renal ablation group (STZ-UX group). At the end of the 8th week after the construction of the model, immunohistochemistry detected MsrB1 expression and distribution in the kidney tissues. The mRNA and protein levels of MsrB1 were determined by real-time PCR and Western blotting. The levels of oxidative stress in the kidneys of four groups were measured by the kits of malondialdehyde (MDA), protein carbonyl (PC) and total sulfhydryl groups (TSH). Results MsrB1 was located in the nucleus and cytoplasm of the renal tubular epithelial cells in mice. Compare with NC group, the mRNA and protein levels of MsrB1 and the content of TSH in the kidneys of STZ group and STZ-UX group were lower, the contents of MDA and PC were higher (P<0.05) and STZ-UX group was more obvious; there was no significant change in UX group (P>0.05). Correlation analysis showed that in the STZ group and STZ-UX group, MsrB1 protein expressions were negatively correlated with MDA and PC (P<0.05), and positively correlated with TSH levels (P<0.05). Conclusion The expression of MsrB1 decreases significantly in the kidneys of STZ-induced diabetic mice, which may play an important role in the oxidative stress of diabetic nephropathy.

Key words: Methionine sulfoxide reductase B1, Oxidative stress, C57BL/6 mice, Diabetic nephropathy

中图分类号: 

  • R692
[1] Stanton R C. Oxidative stress and diabetic kidney disease[J]. Curr Diab Rep, 2011, 11(4): 330-336.
[2] Novoselov S V, Kim H Y, Hua D, et al. Regulation of selenoproteins and methionine sulfoxide reductases A and B1 by age, calorie restriction, and dietary selenium in mice[J]. Antioxid Redox Signal, 2010, 12(7): 829-838.
[3] Hawse J R, Hejtmancik J F, Horwitz J, et al. Identification and functional clustering of global gene expression differences between age-related cataract and clear human lenses and aged human lenses[J]. Exp Eye Res, 2004, 79(6): 935-940.
[4] Hoffmann F W, Hashimoto A S, Lee B C, et al. Hoffmann Specific antioxidant selenoproteins are induced in the heart during hypertrophy[J]. Arch Biochem Biophys, 2011, 512(1): 38-44.
[5] Pabbidi R M, Cao D S, Parihar A, et al. Direct role of streptozotocin in inducing thermal hyperalgesia by enhanced expression of transient receptor potential vanilloid 1 in sensory neurons[J]. Mol Pharmacol, 2008, 73(3): 995-1004.
[6] Chow F Y, Nikolic-Paterson D J, Ozols E, et al. Monocyte chemoattractant protein-1 promotes diabetic renal injury in streptozotocin-treated mice[J]. Kidney Int, 2006, 69(1): 73-80.
[7] Tesch G H, Nikolic-Paterson D J. Recent insights into experimental mouse models of diabetic nephropathy[J]. Nephron Exp Nephrol, 2006, 104(2): 57-62.
[8] 李竹青, 吴伶艳, 乐国伟, 等.氧化酪蛋白对小鼠血液和消化器官氧化损伤的影响[J].营养学报, 2013, 35(1): 39-47. LI Zhuqing, WU Lingyan, LE Guowei, et al. Effect of oxidized casein on the oxidative damage of blood and digestive organs in mice[J]. Acta Nutrimenta Sinica, 2013, 35(1): 39-47.
[9] Kaushik P, Kaushik D, Yadav J, et al. Protective effect of Alpinia galanga in STZ induced diabetic nephropathy[J]. Pak J Biol Sci, 2013, 16(16): 804-811.
[10] Hawkes W C, Alkan Z. Regulation of redox signaling by selenoproteins[J]. Biol Trace Elem Res, 2010, 134(3): 235-251.
[11] Beisswenger P J, Howell S K, Russell G, et al. Detection of diabetic nephropathy from advanced glycation endproducts (AGEs) differs in plasma and urine, and is dependent on the method of preparation[J]. Amino Acids, 2014, 46(2): 311-319.
[12] Kim H Y, Gladyshev V N. Different catalytic mechanisms in mammalian selenocysteine-and cysteine-containing methionine-R-sulfoxide reductases[J]. PLoS Biol, 2005, 3(12): 375.
[13] Moskovitz J, Stadtman E R. Selenium-deficient diet enhances protein oxidation and affects methionine sulfoxide reductase (MsrB) protein level in certain mouse tissues[J]. Proc Natl Acad Sci U S A, 2003, 100(13): 7486-7490.
[14] Novoselov S V, Kim H Y, Hua D, et al. Regulation of Selenoproteins and Methionine Sulfoxide Reductases A and B1 by Age, Calorie Restriction, and Dietary Selenium in Mice[J]. Antioxid Redox Signal, 2010, 12(7): 829-838.
[15] Fomenko D E, Novoselov S V, Natarajan S K, et al. MsrB1 (methionine-R-sulfoxide reductase 1) knock-out mice: roles of MsrB1 in redox regulation and identification of a novel selenoprotein form[J]. Biol Chem, 2009, 284(9): 5986-5993.
[1] 张宝文,雷香丽,李瑾娜,罗湘俊,邹容. miR-21-5p靶向调控TIMP3抑制2型糖尿病肾病小鼠肾脏系膜细胞增殖及细胞外基质堆积[J]. 山东大学学报 (医学版), 2020, 1(7): 7-14.
[2] 陈志新,王颖,曹新冉, 黑乃豪,李俊龙,董波,关广聚. 非肽类Ang(1-7)受体激动剂AVE0991对大鼠糖尿病肾病的保护作用[J]. 山东大学学报（医学版）, 2016, 54(10): 29-33.
[3] 杨倩倩,孙高英,曹智新,尹海燕,王海波,李建峰. NLRX1在C57BL/6小鼠耳蜗毛细胞内的表达[J]. 山东大学学报（医学版）, 2016, 54(1): 11-16.
[4] 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.
[5] 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.
[6] 李少伟, 刘宗正, 刘春霞, 张焱如, 周欢敏. 口服富氢水对小鼠脂肪肝缺血再灌注损伤的保护作用[J]. 山东大学学报（医学版）, 2015, 53(1): 10-15.
[7] 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.
[8] 黄静, 胥莹, 刘毅, 辛玮, 赵胥, 刘蕾, 完强. 乙酰辅酶A羧化酶2表达下调对高糖培养的人肾小管上皮细胞脂质沉积和间充质转化的影响[J]. 山东大学学报（医学版）, 2014, 52(7): 16-21.
[9] 刘莹1，2，王志蕴1，2，解园星1，2，席振创1，2. 瑞舒伐他汀对ApoE-/-小鼠心肌SIRT1信号通路的影响[J]. 山东大学学报（医学版）, 2014, 52(3): 7-10.
[10] 张锦航1，张鲁伟1，刘新农2，田军1. Db/db小鼠肾脏中Tribble3的表达及其与肾脏纤维化的关系[J]. 山东大学学报（医学版）, 2014, 52(2): 38-43.
[11] 王福1，刘善文1，李彬2，耿海华3，孙帅1，李睿1，肖洁1，季晓平1 . rhEPO对氧化应激时心肌细胞及心肌梗死后心脏的保护作用[J]. 山东大学学报(医学版), 2013, 51(7): 1-5.
[12] 毕大鹏1，嵇高德1，张洪星2 . 通心络胶囊对早期糖尿病肾病患者胱抑素C的影响[J]. 山东大学学报(医学版), 2013, 51(7): 67-69.
[13] 王杰1，常相帝1，李冰1，肖晓燕1，张扬1，甄军晖2，姜虹3，胡昭1. 霉酚酸酯对糖尿病大鼠肾小管上皮细胞转分化的影响[J]. 山东大学学报(医学版), 2012, 50(6): 14-19.
[14] 常相帝1，王杰1，李冰1，甄军晖2，姜虹3，胡昭1. FK506对早期糖尿病肾病大鼠足细胞损伤的保护作用[J]. 山东大学学报(医学版), 2012, 50(6): 20-25.
[15] 杜月娟1，刘元涛2，卢圣霞1，刘晔1，齐文文1，傅余芹1. 冬虫夏草菌丝对糖尿病大鼠肾脏DKK1、β-catenin表达的影响[J]. 山东大学学报(医学版), 2012, 50(6): 26-.
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