【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≥25mmol·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,16d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。更多还原

【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 pancreaticβcells combined with streptozotocin(STZ)-induced type 1diabetes model.Methods The experiment was divided into four groups:knockout mice group(LLc knockout group),using the homozygotes(LLc:LL+Cre)producted by pancreaticβcell-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 16d 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 Pancreaticβcell GHR gene knockout has no effect on the blood glucose and the function ofβcells in the mice with STZ-induced type 1 diabetes.更多还原