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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

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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.
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