吉林大学学报(医学版)

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胰腺β细胞生长激素受体基因敲除对STZ诱发1型糖尿病小鼠的影响

任国君1,孙杰2,申风娟3,史春红1,于涛2,姜如娇2,吴英杰2,孙捷1   

  1. (1.吉林大学第一医院干部病房,吉林 长春 130021;2.大连医科大学中西医结合学院(研究院),辽宁 大连116044;3.大连医科大学附属第一医院内分泌科,辽宁 大连 116011)
  • 收稿日期:2013-12-05 出版日期:2014-07-28 发布日期:2014-07-28
  • 通讯作者: 孙捷 E-mail:(Tel:0431-88782657,E-mail:sunjiesusan@126.com)
  • 作者简介:任国君(1988-),女,山东省日照市人,在读医学硕士,主要从事老年心血管系统疾病及代谢综合征的基础与临床研究。
  • 基金资助:

    吉林省科技厅国际科技合作项目资助课题(20120709)

Influence of growth hormone receptor gene knockout in pancreatic β cells in STZ-induced type 1 diabetes in mice

REN Guo-jun1,SUN Jie2,SHEN Feng-juan3,SHI Chun-hong1,YU Tao2,JIANG Ru-jiao2,WU Ying-jie2,SUN Jie1   


  1.  (1.Department of Cadre Ward,First Hospital,Jilin University,Changchun 130021,China;2.College of Combination of Chinese Traditional and Western Medicine,Dalian Medical University,Dalian 116044,China;3.Department of Endocrinology,First Affilliated Hospital,Dalian Medical University,Dalian 116011,China)
  • Received:2013-12-05 Online:2014-07-28 Published:2014-07-28

摘要:

目的:利用胰腺β细胞组织特异性生长激素受体(GHR)基因敲除小鼠结合链脲佐菌素(STZ )诱导1型糖尿病模型,从基因水平研究胰腺β细胞GHR缺失对1型糖尿病的影响。方法: 实验小鼠分4组,包括LLc对照组[胰腺β细胞特异敲除GHR小鼠(βGHRKO,LLc)、LL对照组[含有GHR等位基因纯合子小鼠(LL)]、LLc STZ组及LL STZ组(LLc 小鼠和LL小鼠分别给予STZ注射造模),小鼠餐后血糖≥25 mmol•L-1为造模成功。对小鼠进行葡萄糖耐量实验(GTT)、小鼠胰腺组织HE染色和免疫组织化学检测。结果:STZ注射后,LL STZ组和LLc STZ组小鼠血糖出现上升趋势,16 d后达到1型糖尿病诊断标准。GTT,LL STZ组和LLc STZ组小鼠血糖值分别较LL对照组和LLc 对照组小鼠血糖值明显升高(P<0.05),HE染色,与LL 对照组比较,LLc 对照组小鼠胰岛形态及结构无明显变化;LL STZ和LLc STZ组小鼠胰岛萎缩,β细胞数量明显减少。免疫组织化学检测,LL STZ组较LL对照组小鼠胰岛素分泌显著减少,LLc STZ组较LLc 对照组小鼠胰岛素分泌显著减少。结论:在STZ诱导1型糖尿病条件下,胰腺β细胞GHR基因敲除对1型 糖尿病小鼠血糖及β细胞功能无明显影响。

关键词: 生长激素;生长激素受体;糖尿病, 1型;胰岛素分泌细胞;基因敲除;疾病模型, 动物

Abstract:

Abstract:Objective
To investigate the influence of  tissue-specific growth hormone receptor(GHR) deficiency   in  type 1 diabetes in the mice at  the gene level using pancreatic β cells   combined with streptozotocin (STZ)-induced type 1 diabetes model.Methods The experiment was  divided into four groups:knockout mice group(LLc knockout group),using the homozygotes(LLc:LL+Cre)producted by  pancreatic β cell- specific expressed  recombinant enzyme  mice(RIP-Cre) and Cre-LoxP system modified GHR  mice (Floxed,LL);LL control group,containing Floxed GHR allele homozygous mice(LL);LLc STZ group and LL STZ group(STZ was used for inducing type 1 diabetes model mice).The mice with feeding glucose≥25 mmol•L-1 were considered to be successful models.The Glucose Tolerance Test (GTT), pancreas tissue HE staining and immunohistochemistry were performed in the mice.Results The blood glucose of the mice in LL STZ group and LLc STZ group and LLc STZ group were increased after injection of STZ and the models achieved the diagnostic criteria for diabetes 16 d later.The results of GTT showed that compared with LLc control group and LLc knockout group,the blood glucose levels of the mice in LL STZ and LLc STZ groups were increased (P<0.05).There was no significant change of morphology and structure  of islets between LL control group and LLc knockout group detected by HE staining.The immunohistochemistry results showed that the  insulin level of the mice  in LL STZ group was significantly reduced compared with LL control group;the insulin level of the mice in LLc STZ group was reduced compared  with  LLc control group.Conclusion  Pancreatic β cell GHR gene knockout has no  effect on the  blood glucose and the function of β cells in the mice with STZ-induced type 1 diabetes.

Key words: growth hormone;growth hormone receptor;diabetes, type 1;insulin-secreting cells;gene , knockout;disease model,animal 

中图分类号: 

  • R335.6