[1]刘艳,田秀标,韩颖,等.血管紧张素1-7与糖尿病及糖尿病肾脏 内质网应激关系的研究[J].国际内分泌代谢杂志,2016,36(03):157-161.[doi:10.3760/cma.j.issn.1673-4157.2016.03.04]
　Liu Yan*,Tian Xiubiao,Han Ying,et al.Relationship between angiotensin 1-7, diabetes and endoplasmic reticulum stress of diabetic kidney[J].International Journal of Endocrinology and Metabolism,2016,36(03):157-161.[doi:10.3760/cma.j.issn.1673-4157.2016.03.04]
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血管紧张素1-7与糖尿病及糖尿病肾脏 内质网应激关系的研究()
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《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
36
期数:
2016年03期
页码:
157-161
栏目:
论著
出版日期:
2016-05-20

文章信息/Info

Title:
Relationship between angiotensin 1-7, diabetes and endoplasmic reticulum stress of diabetic kidney
作者:
刘艳; 田秀标; 韩颖; 石节丽; 徐福娟; 高鹏飞; 张秋羽; 谢云
300070 天津医科大学代谢病医院糖尿病神经内科,卫生部激素与发育重点实验室(刘艳,谢云); 300280 天津海滨人民医院内分泌科(刘艳,田秀标,韩颖,石节丽,徐福娟,高鹏飞),消化科(张秋羽)
Author(s):
Liu Yan*;  Tian Xiubiao;  Han Ying;  Shi Jieli;  Xu Fujuan;  Gao Pengfei;  Zhang Qiuyu;  Xie Yun.
*Department of Diabetic Neurology, Key Laboratory of Hormones and Development(Ministry of Health), The Metabolic Diseases Hospital of Tianjin Medical University, Tianjin 300070, China
关键词:
血管紧张素1-7;  糖尿病;  糖尿病肾病;  内质网应激
Keywords:
Angiotensin 1-7;  Diabetes mellitus;  Diabetic kidney disease;  Endoplasmic reticulum stress
DOI:
10.3760/cma.j.issn.1673-4157.2016.03.04
摘要:
目的 调查糖尿病患者血管紧张素1-7(Ang1-7)水平和评价Ang1-7对糖尿病大鼠肾脏内质网应激的影响。方法 选取2014年12月至2015年6月于天津市海滨人民医院未诊断为糖尿病的95名体检人员为研究对象,所有受试者均进行口服葡萄糖耐量试验,根据血糖水平分为健康组(n=31)、血糖异常组(n=32)和糖尿病组(n=32)。检测其体重、腰围、血压、肝功能、肾功能、Ang1-7、血管紧张素转换酶(ACE)2等指标。分析血糖与Ang1-7、ACE2的相关性。另外,选取10只150～200 g健康雄性Sprague-Dawley(SD)大鼠,通过腹腔注射链脲佐菌素制备糖尿病模型,全部成功,根据随机数字法,分为糖尿病组和Ang1-7组,每组5只,分别皮下泵入生理盐水和Ang1-7,另选取5只健康SD大鼠作为正常组。干预2周后处死所有大鼠,留取肾组织标本,Western印迹和实时荧光定量PCR检测葡萄糖调节蛋白78(GRP78)、转录活性因子4(ATF4)、增强子结合蛋白同源蛋白(CHOP)水平。结果 与健康组相比,血糖异常组和糖尿病组甘油三酯、ACE2、Ang1-7水平均升高; 糖尿病组较健康组升高更明显(F=5.57,6.12,5.44, P均<0.01)。Pearson相关分析显示,糖尿病组、血糖异常组的空腹血糖、餐后血糖均与Ang1-7呈正相关(r=0.69,0.45,P均<0.01; r=0.54,0.52,P均<0.01)。与正常组相比,糖尿病组大鼠肾脏GRP78、ATF4和CHOP水平明显升高; 与糖尿病组相比,Ang1-7组GRP78、ATF4和CHOP水平明显下降(t=20.3,25.7,19.6,P均<0.05)。与同期正常组比较,糖尿病组大鼠肾组织GRP78、ATF4和CHOP的mRNA均显著上调。与糖尿病组比较,Ang1-7组大鼠肾组织GRP78、ATF4和CHOP的mRNA的表达受到显著抑制(t=15.1,11.6,12.3,P均<0.05)。结论 Ang1-7水平随着受试者血糖浓度的升高而升高,另外,Ang1-7可降低糖尿病大鼠肾脏内质网应激蛋白水平。
Abstract:
Objective To investigate the level of angiotensin 1-7(Ang1-7)in patients with diabetes, and to study the effects of Ang1-7 on endoplasmic reticulum(ER)stress in the kidney of diabetic rats. Methods Ninety-five subjects without diagnosed diabetes were screened in Tianjin Seaside People's Hospital from December 2014 to June 2015. Oral glucose tolerance test was implemented. According to the level of blood glucose, subjects were divided into three groups: healthy group(n=31), impaired glucose group(n=32), and diabetes group(n=32). Body weight, waist circumference, blood pressure, liver function, renal function, Ang1-7, angiotensin-converting enzyme(ACE)2 and other indicators were detected. Relationship between blood glucose and Ang1-7 and ACE2 were analyzed. In addition, ten healthy male Sprague-Dawley(SD)rats(150-200 g)were chosen to induce diabetes through intraperitoneal injection of streptozotocin, and all succeeded. Ten diabetic rats were randomly divided into Ang1-7 group and diabetes group according to the random number method, and pumped into Ang1-7 or saline solution, respectively, with five rats in each group. Other five healthy SD rats were chosen as normal group. All rats were sacrificed after intervention for two weeks. Kidney specimens were used to test the level of ER stress proteins, including glucose-regulated protein(GRP)78, activity of transcription factor(ATF)4, enhancer binding protein homologous protein(CHOP), by Western Blotting and Real-time Quantitative PCR. Results Compared with healthy group, levels of triglycerides, ACE2, Ang1-7 in impaired glucose group and diabetes group were increased,especially the diabetes group(F=5.57,6.12,5.44, all P<0.01). Pearson correlation analysis showed that fasting blood glucose and postprandial blood glucose in diabetes group and impaired glucose group were positive correlated with Ang1-7(r=0.69,0.45,all P<0.01; r=0.54,0.52,all P<0.01). Compared with normal group, levels of GRP78, ATF4, and CHOP were increased significantly in diabetes group; compared with diabetes group, levels of GRP78, ATF4, and CHOP were significantly reduced in Ang1-7 group(t=20.3, 25.7, 19.6, all P<0.05). Compared with normal group, mRNA levels of GRP78, ATF4, and CHOP were increased significantly in diabetes group; compared with diabetes group, levels of GRP78, ATF4, and CHOP were significantly reduced in Ang1-7 group(t=15.1, 11.6, 12.3, all P<0.05). Conclusions The level of Ang1-7 evelates with the increase of blood glucose concentration in subjects. Ang1-7 reduces ER stress in the kidney of diabetic rats.

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更新日期/Last Update: 2016-05-20