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） ›› 2016, Vol. 54 ›› Issue (10): 29-33.doi: 10.6040/j.issn.1671-7554.0.2015.1184

• • 上一篇    下一篇

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

陈志新1,2,王颖3,曹新冉2, 黑乃豪2,李俊龙2,董波2,关广聚1   

  1. 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;2.山东大学附属省立医院心内科, 山东 济南 250021;3.德州市立医院老年科, 山东 德州 253000
  • 收稿日期:2015-11-27 出版日期:2016-10-10 发布日期:2016-10-10
  • 通讯作者: 关广聚. E-mail:guangj@sdu.edu.cn; 董波. E-mail:bodong@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(81170207,81570653);山东省医药卫生科技发展计划(2011HD004);济南市高校院所自主创新计划(200906011-1)

Evaluation of the protective effect of AVE0991 on streptozotocin-induced diabetic nephropathy rats

CHEN Zhixin1,2, WANG Ying3, CAO Xinran2, HEI Naihao2, LI Junlong2, DONG Bo2, GUAN Guangju1   

  1. 1. Nephrology Research Institute, Shandong University, Department of Nephrology, Second Hospital of Shandong University, Jinan 250033, Shandong, China;
    2. Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
    3. Department of Geriatrics, Municipal Hospital of Dezhou, Dezhou 253000, Shandong, China
  • Received:2015-11-27 Online:2016-10-10 Published:2016-10-10

PDF (PC)

246

摘要： 目的 探究非肽类Ang(1-7)受体激动剂AVE0991对链脲佐菌素(STZ)诱导的大鼠糖尿病肾病(DN)的保护作用。 方法 30只Wistar大鼠随机分为3组:正常对照组(NC组)、糖尿病肾病组(DN组)、AVE0991处理组(AVE组),每组10只。DN组与AVE组腹腔注射STZ(65 mg/kg),STZ注射8周后,给予AVE组AVE0991灌胃处理,NC组及DN组取等量生理盐水灌胃,连续灌胃4周。12周末收集标本,检测各项生理生化指标;高碘酸-希夫(PAS)及免疫组化观察各组肾脏病理变化;实时荧光定量PCR及酶联免疫吸附实验(ELISA)法分别检测白介素1β(IL-1β)、白介素6(IL-6)和肿瘤坏死因子α(TNF-α)的mRNA及蛋白水平变化。 结果 与NC组相比,DN组与AVE组大鼠血肌酐、24 h尿蛋白定量、肾质量体质量比明显升高,肾小球硬化指数、胶原Ⅰ(CollagenⅠ)表达量、炎症因子IL-1β、IL-6、TNF-α mRNA及蛋白水平明显上升。AVE组与DN组相比,大鼠血肌酐、24 h尿蛋白定量、肾小球硬化指数、CollagenⅠ表达量及肾组织炎症因子IL-1β、IL-6、TNF-α mRNA及蛋白表达均明显降低(P<0.01)。 结论 AVE0991可以降低大鼠DN的纤维化及炎症水平。

关键词: 血管紧张素(1-7)受体激动剂, 糖尿病肾病, AVE0991, 血管紧张素1-7, Wistar, 大鼠

Abstract: Objective To explore the protective effect of AVE0991, a non-peptide Ang(1-7)receptor agonist, on rat models of diabetic nephropathy. Methods A total of 30 male Wistar rats were randomly divided into 3 groups: normal control group(NC group, n=10), streptozotocin(STZ)induced diabetic nephropathy group(DN group, n=10)and AVE0991 treatment group(AVE group, n=10). After the DN group and AVE group received intraperitoneal injection of streptozotocin(STZ)65 mg/kg for 8 weeks, the AVE group received AVE0991 via gavage, and the DN and NC groups received normal saline of the same amount for 4 weeks continuously. Then the renal functional and bio-chemical parameters were measured. Renal pathological changes of each group were observed by Periodic Acid Schiff(PAS)staining and immunohistochemistry. The mRNA protein levels of IL-1β, IL-6, and TNF-α were determined by quanti- 山 东 大 学 学 报 (医 学 版)54卷10期 -陈志新,等.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 \=-fication real-time PCR. The concentrations of IL-1β, IL-6 and TNF-α protein levels were measured by ELISA. Results Compared with the NC group, the DN and AVE groups exhibited increased serum creatinine, 24 h-urine protein excretion, glomerulosclerositic index, expression of CollagenⅠas well as increased mRNA protein levels of IL-1β, IL-6 and TNF-α. Treatment of diabetic nephropathy with AVE0991 exhibited renal protective effect, as evidenced by a significant decrease in serum creatinine, 24 h-urine protein excretion, glomerulosclerositic index and downregulation of inflammatory factors(IL-1β, IL-6, TNF-α). Conclusion AVE0991 may have therapeutic potential in diabetic nephropathy by alleviating fibrosis and inflammation in kidney.

Key words: AVE0991, Ang(1-7)receptor agonist, Diabetes nephropathy, Rats, Wistar, Ang(1-7)

中图分类号: 

  • R587.2
[1] Kamiyama M, Urushihara M, Morikawa T, et al. Oxidative stress angiotensinogen renin-angiotensin system axis in patients with diabetic nephropathy [J]. Int J Mol Sci, 2013, 14(11):23045-23062.
[2] Passos-Silva DG, Verano-Braga T, Santos RA, et al. Angiotensin-(1-7): beyond the cardio-renal actions[J]. Clin Sci(Lond), 2013, 124(7):443-456.
[3] 吴宏力, 鲁军, 佘星星, 等. 血管紧张素转换酶2-血管紧张素(1-7)-Mas轴的血压调控作用研究进展[J]. 中华高血压杂志, 2014, 22(6):528-532.
[4] Liu CX, Hu Q, Wang Y, et al. Angiotensin-converting enzyme(ACE)2 overexpression ameliorates glomerular injury in a rat model of diabetic nephropathy: a comparison with ACE inhibition[J]. Mol Med, 2011, 17(1-2):59-69.
[5] Mizuiri S, Aoki T, Hemmi H, et al. Urinary angiotensin-converting enzyme 2 in patients with CKD[J]. Nephrology(Carlton), 2011, 16(6):567-572.
[6] Mori J, Patel VB, Ramprasath T, et al. Angiotensin 1-7 mediates renoprotection against diabetic nephropathy by reducing oxidative stress, inflammation, and lipotoxicity [J]. Am J Physiol Renal Physiol, 2014, 306(8):F812-821.
[7] Giani JF, Burghi V, Veiras LC, et al. Angiotensin-(1-7)attenuates diabetic nephropathyin Zucker diabetic fatty rats[J]. Am J Physiol Renal, 2012, 302(12):F1606-1615.
[8] Liu RM, Gaston Pravia KA. Oxidative stress and glutathione in TGFbeta-mediated fibrogenesis[J]. Free Radic Biol Med, 2010, 48(1):1-15.
[9] Liu GC, Oudit GY, Fang F, et al. Angiotensin-(1-7)-induced activation of ERK1/2 is cAMP/protein kinase A-dependent in glomerular mesangial cells [J]. Am J Physiol Renal Physiol, 2012, 302:F784-F790.
[10] Zhang K, Meng X, Li D, et al. Angiotensin(1-7)attenuates the progression of streptozotocin-induced diabetic renal injury better than angiotensin receptor blockade[J]. Kidney Int, 2015, 87(2):359-369.
[11] Santos RA, Ferreira AJ. Pharmacological effects of AVE 0991, a nonpeptide angiotensin-(1-7)receptor agonist [J]. Cardiovasc Drμg Rev, 2006, 24(3-4):239-246.
[12] Grace JA, Klein S, Herath CB, et al. Activation of the MAS receptor by angiotensin-(1-7)in the renin-angiotensin system mediates mesenteric vasodilatation in cirrhosis[J]. Gastroenterology, 2013, 145(4):874-884.
[13] Wada J, Makino H. Inflammation and the pathogenesis of diabetic nephropathy [J]. Clin Sci(Lond), 2013, 124(3):139-152.
[14] Tesch GH. Macrophages and diabetic nephropathy [J]. Semin Nephrol, 2010, 30(3):290-301.
[15] Nguyen D, Ping F, Mu W, et al. Macrophage accumulation in human progressive diabetic nephropathy [J]. Nephrology(Carlton), 2006, 11(3):226-231.
[16] Barroso LC, Silveira KD, Lima CX, et al. Renoprotective effects of AVE0991, a nonpeptide mas receptor agonist, in experimental acute renal injury[J]. Int J Hypertens, 2012, 2012:808726. doi: 10.1155/2012/808726. Epub 2012 Jan 29.
[17] da Silveira KD, Coelho FM, Vieira AT, et al. Anti-inflammatory effects of the activation of the angiotensin-(1-7)receptor, MAS, in experimental models of arthritis [J]. J Immunol, 2010, 185(9):5569-5576.
[1] 吴逸南 葛志明 李方 贺红 姜虹 张运. 自发性高血压大鼠肾脏血管紧张素转换酶2的表达[J]. 山东大学学报(医学版), 2209, 47(6): 5-.
[2] 祝林 胡三元 张光永 丁祥就. 前列腺素E2对阻塞性黄疸大鼠小肠粘膜形态的保护作用[J]. 山东大学学报(医学版), 2209, 47(6): 12-.
[3] 孙涛 张道来 谢珊珊 王玉卓 冯玉新 辛华. 酒精对原代培养的神经前体细胞间隙连接蛋白43表达的影响[J]. 山东大学学报(医学版), 2209, 47(6): 20-.
[4] 张道来 孙涛 谢珊珊 王玉卓 赵玲 冯玉新 辛华. 体外原代培养胎鼠大脑皮层神经元NMDAR1亚基表达的发育性变化[J]. 山东大学学报(医学版), 2209, 47(6): 28-32.
[5] 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.
[6] 张亮,徐敏,庄向华,娄福臣,娄能俊,吕丽,郭文娟,郑凤杰,陈诗鸿. 内质网应激与凋亡在糖尿病周围神经病变中的表达变化[J]. 山东大学学报（医学版）, 2017, 55(8): 13-17.
[7] 刘芳,乔蕾,陈文超,杨丽娜. 大蒜素后处理对大鼠心肌缺血-再灌注损伤的保护作用[J]. 山东大学学报（医学版）, 2017, 55(7): 6-11.
[8] 谢海滨,武群政,刘少壮,黄鑫,程玉刚,胡三元,张光永. 肝线粒体相关内质网膜在袖状胃切除术改善糖尿病大鼠胰岛素敏感性中的作用[J]. 山东大学学报（医学版）, 2017, 55(10): 36-40.
[9] 陈怡憓,刘学蔚,侯绪浩,孙钦峰. 醛化白及多糖/羟丙基壳聚糖/纳米珍珠层粉复合材料促下颌骨缺损修复的动物实验研究[J]. 山东大学学报（医学版）, 2016, 54(6): 7-11.
[10] 李红志,刘静,宋岩,迟令懿,刘玉光. 利拉鲁肽对脊髓损伤修复作用的探讨[J]. 山东大学学报（医学版）, 2016, 54(4): 1-5.
[11] 任宝鑫,马云峰,刘殿伟,李卓,姜勇. Wnt3a在大鼠蛛网膜下腔出血后早期脑损伤中对神经细胞自噬和凋亡的影响[J]. 山东大学学报（医学版）, 2016, 54(10): 11-15.
[12] 赵蕙琛,柴家超,张亮,袁明振,彭力,刘元涛. 糖尿病大鼠阴茎海绵体硫化氢含量及其合成酶表达的变化[J]. 山东大学学报（医学版）, 2016, 54(10): 25-28.
[13] 张东青, 王勇, 陈守臻, 朱耀丰, 史本康. 糖尿病大鼠尿道α1肾上腺素能受体与神经生长因子表达的改变及其对尿道功能的影响[J]. 山东大学学报（医学版）, 2015, 53(9): 30-34.
[14] 冯潇雨, 张洪美, 车选强, 康东红. 成骨细胞刺激因子对去卵巢骨质疏松大鼠的治疗效果[J]. 山东大学学报（医学版）, 2015, 53(7): 8-12.
[15] 姜蕾, 张磊, 梁江久. 长链非编码RNA在压力超负荷引起的大鼠心肌肥厚中的差异表达[J]. 山东大学学报（医学版）, 2015, 53(5): 21-26.
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