[1]丰树焕,张东铭,乐婷,等.妊娠期糖尿病大鼠胰腺组织中p-PERK、ATF4和CHOP蛋白的表达[J].郑州大学学报(医学版),2015,(04):496-499.
 FENG Shuhuan,ZHANG Dongming,LE Ting,et al.Expressions of pPERK,ATF4 and CHOP protein in rat model of gestational diabetes mellitus[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2015,(04):496-499.
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妊娠期糖尿病大鼠胰腺组织中p-PERK、ATF4和CHOP蛋白的表达()
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《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2015年04期
页码:
496-499
栏目:
论著
出版日期:
2015-07-20

文章信息/Info

Title:
Expressions of pPERK,ATF4 and CHOP protein in rat model of gestational diabetes mellitus
作者:
丰树焕1张东铭1乐婷2张苏河1#付艳芹1
1)郑州大学第二附属医院内分泌科 郑州 4500142)郑州大学第二附属医院神经内科 郑州 450014
Author(s):
FENG Shuhuan1ZHANG Dongming1LE Ting2ZHANG Suhe1FU Yanqin1
FENG Shuhuan1),ZHANG Dongming1),LE Ting2),ZHANG Suhe1),FU Yanqin1)
关键词:
大鼠内质网应激蛋白激酶R样内质网激酶C/EBP同源蛋白β细胞凋亡
Keywords:
ratendoplasmic reticulum stressPERKCHOPβ cell apoptosis
分类号:
R587.1
文献标志码:
A
摘要:
目的:探讨磷酸化蛋白激酶R样内质网激酶(pPERK)、C/EBP同源蛋白(CHOP)、ATF4蛋白的表达与高脂高糖诱导的妊娠期糖尿病大鼠胰岛β细胞凋亡的关系。方法:30只雌性SD大鼠分为模型组(高脂高糖喂养)和对照组(普食喂养),每组15只,妊娠第21天行静脉糖耐量及静脉胰岛素释放实验;取胰腺组织行HE染色和病理组织学观察,TUNEL法检测胰岛β细胞凋亡情况,免疫组化法检测胰腺组织中pPERK蛋白的表达,Western blot检测胰腺组织中ATF4及CHOP蛋白的表达。结果:模型组大鼠第一时相胰岛素分泌受抑制,胰岛素分泌峰值延迟;病理组织学可见模型组大鼠胰岛形态欠规则,数目减少不明显,部分细胞空泡变性,毛细血管扩张、充血,有出血发生。模型组大鼠胰腺组织细胞凋亡率较对照组升高(t= 21.164,P<0.001)。与对照相比,模型组大鼠胰腺组织pPERK、ATF4及CHOP蛋白表达水平明显升高(t= 44.178、49.249、39.664,P<0.001);模型组大鼠胰腺组织中ATF4与CHOP蛋白的表达呈正相关(r=0.810,P=0.004)。结论:PERK、ATF4可能参与妊娠期糖尿病大鼠胰岛β细胞凋亡的发生。
Abstract:
Aim: To investigate the relationship between the activation of pPERK,ATF4 and CHOP protein and islet β cell apoptosis of pregnant rats with high sucrose and fat diet.Methods: Thirty healthy female SD rats were allocated into two groups randomly: control group(n=15) and gestational diabetes mellitus(GDM) model group(n=15).Twentyone days after gestation,intravenous glucose tolerance test(IVGTT) and intravenous insulin releasing test(IVIRT) were performed;the pancreas was removed for examination of morphological and ultra structural changes; the islet β cell apoptosis index was calculated by TUNEL;the expression of pPERK in pancreatic tissue was analyzed by immunohistochemistry;the expressions of ATF4 and CHOP protein were analyzed by Western blot.Results: The firstphase insulin secretion of rats in the GDM model group was inhibited,and the insulin secretion peak was delayed;the islet morphology was not regular,the reducing was not obvious,some cells degenerated,blood capillaries dilated,and there was hyperemia or bleeding occurred in the GDM model group by means of HE staining;the apoptotic rate increased in the GDM model group(t= 21.164,P<0.001);compared with control group,the level of pPERK,ATF4,and CHOP in pancreatic tissue increased significantly in the GDM model group(t=44.178,49.249,and 39.664,P<0.05).Correlation analysis showed that the expression level of ATF4 was positively correlated with CHOP protein in islet tissue from rats in the GDM model group(r=0.810,P=0.004).Conclusion: The activation expressions of ATF4 and PERK protein may participate in apoptosis of pancreatic β cells in GDM rats induced by high sucrose and fat diet.

参考文献/References:

[1]郭啸华,刘志红,李恒,等.高糖高脂饮食诱导的2型糖尿病大鼠模型及其肾病特点[J].中国糖尿病杂志,2002,10(5):35
[2]Sinzato YK,Volpato GT,Iessi IL,et al.Neonatally induced mild diabetes in rats and its effect on maternal, placental, and fetal parameters[J].Exp Diabetes Res,2012,2012:108163
[3]Sonenberg N,Hinnebusch AG.Regulation of translation initiation in eukaryotes:mechanisms and biological targets[J].Cell,2009,136(4):731
[4]EvansMolina C,Hatanaka M,Mirmira RG.Lost in translation: endoplasmic reticulum stress and the decline of βcell health in diabetes mellitus[J].Diabetes Obes Metab,2013,15(Suppl 3):159
[5]Van Der Kallen CJ,Van Greevenbroek MM,Stehouwer CD,et al.Endoplasmic reticulum stressinduced apoptosis in the development of diabetes: is there a role for adipose tissue and liver?[J].Apoptosis,2009,14(12):1424
[6]Toth A,Nickson P,Mandl A,et al.Endoplasmic reticulum stress as a novel therapeutic target in heart diseases[J].Cardiovasc Hematol Disord Drug Targets,2007,7(3):205
[7]Cnop M,Foufelle F,Velloso LA.Endoplasmic reticulum stress, obesity and diabetes[J].Trends Mol Med,2012,18(1):59
[8]Fels DR,Koumenis C.The PERK/eIF2alpha/ATF4 module of the UPR in hypoxia resistance and tumor growth[J].Cancer Biol Ther,2006,5(7):723
[9]Eizirik DL,Cardozo AK,Cnop M.The role for endoplasmic reticulum stress in diabetes mellitus[J].Endocr Rev,2008,29(1):42
[10]Matsumoto H,Miyazaki S,Matsuyama SA,et al.Selection of autophagy or apoptosis in cells exposed to ERstress depends on ATF4 expression pattern with or without CHOP expression[J].Biol Open,2013,2(10):1084

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