GLP-1重组减毒沙门菌对2型糖尿病小鼠的治疗作用

发布时间：2018-03-24 14:32

本文选题：GLP-1　切入点：减毒沙门菌　出处：《安徽医科大学》2017年硕士论文

【摘要】：目的观察重组减毒沙门菌作为GLP-1的基因载体,对2型糖尿病小鼠的治疗作用。方法高脂饲料饲喂4周后予以STZ(链脲佐菌素)构建KM种小鼠2型糖尿病模型[1-4],小鼠分为4组:正常组、模型组、空载组及治疗组,每组10只,分别予以:5%NaHCO_3、5%NaHCO_3、同等剂量的空载减毒沙门菌及GLP-1重组减毒沙门菌灌胃治疗,观察并记录治疗前及治疗后第7、14、21、28天的空腹血糖值及体重变化,分别于治疗后第14天及第28天行OGTT试验,第28天取小鼠胰腺组织,采用HE染色法观察各组小鼠的胰腺组织形态学变化。结果 GLP-1重组减毒沙门菌灌胃治疗2周后,治疗组小鼠的空腹血糖较空载组有明显下降(P0.01),口服葡萄糖耐量也有明显改善(P0.01);治疗4周后,空腹血糖下降更明显(P0.01),口服葡萄糖耐量改善更加明显(P0.01);GLP-1重组减毒沙门菌灌胃治疗后,治疗组小鼠体重下降有明显的改善(P0.01);胰腺HE染色结果显示,治疗组较模型组、空载组小鼠胰腺形态学变化有明显改善。结论 GLP-1重组减毒沙门菌能够降低2型糖尿病小鼠血糖,改善体重下降等糖尿病症状,改善胰岛形态学变化。减毒沙门菌作为基因治疗载体,在2型糖尿病的基因治疗方面,具有巨大的潜在优势。
[Abstract]:Objective to observe recombinant attenuated Salmonella as a gene vector of GLP-1. Methods km type 2 diabetic mice were induced by STZZ (streptozotocin) for 4 weeks. The mice were divided into 4 groups: normal group, model group, no-load group and treatment group, with 10 rats in each group. The rats were treated with 5: 5 NaHCOS3 and NaHCOD 3, and the same dose of non-loaded salmonella and GLP-1 recombinant attenuated salmonella were given intragastrically. The fasting blood glucose and body weight were observed and recorded before and after treatment. The changes of fasting blood glucose and body weight were measured on the 14th day and the 28th day after the treatment, respectively, and the changes of fasting blood glucose and body weight were recorded respectively on the 14th and 28th day after treatment. On the 28th day, the pancreas tissue of mice was taken and observed by HE staining method. Results after 2 weeks of treatment with GLP-1 recombinant attenuated Salmonella, Compared with the control group, the fasting blood glucose in the treatment group decreased significantly (P 0.01) and the oral glucose tolerance was also significantly improved. After 4 weeks of treatment, the decrease of fasting blood glucose was more obvious than that of the control group, and the improvement of oral glucose tolerance was more obvious after oral administration of Salmonella mutans. The results of HE staining showed that the morphological changes of pancreas in the treatment group were significantly improved compared with the model group. Conclusion GLP-1 recombinant attenuated Salmonella can reduce blood glucose in type 2 diabetic mice. As a carrier of gene therapy, attenuated Salmonella has great potential advantages in gene therapy of type 2 diabetes.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1;R450

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