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GLP-1重組減毒沙門菌對2型糖尿病小鼠的治療作用

發(fā)布時間:2018-03-24 14:32

  本文選題:GLP-1 切入點:減毒沙門菌 出處:《安徽醫(yī)科大學(xué)》2017年碩士論文


【摘要】:目的 觀察重組減毒沙門菌作為GLP-1的基因載體,對2型糖尿病小鼠的治療作用。方法 高脂飼料飼喂4周后予以STZ(鏈脲佐菌素)構(gòu)建KM種小鼠2型糖尿病模型[1-4],小鼠分為4組:正常組、模型組、空載組及治療組,每組10只,分別予以:5%NaHCO_3、5%NaHCO_3、同等劑量的空載減毒沙門菌及GLP-1重組減毒沙門菌灌胃治療,觀察并記錄治療前及治療后第7、14、21、28天的空腹血糖值及體重變化,分別于治療后第14天及第28天行OGTT試驗,第28天取小鼠胰腺組織,采用HE染色法觀察各組小鼠的胰腺組織形態(tài)學(xué)變化。結(jié)果 GLP-1重組減毒沙門菌灌胃治療2周后,治療組小鼠的空腹血糖較空載組有明顯下降(P0.01),口服葡萄糖耐量也有明顯改善(P0.01);治療4周后,空腹血糖下降更明顯(P0.01),口服葡萄糖耐量改善更加明顯(P0.01);GLP-1重組減毒沙門菌灌胃治療后,治療組小鼠體重下降有明顯的改善(P0.01);胰腺HE染色結(jié)果顯示,治療組較模型組、空載組小鼠胰腺形態(tài)學(xué)變化有明顯改善。結(jié)論 GLP-1重組減毒沙門菌能夠降低2型糖尿病小鼠血糖,改善體重下降等糖尿病癥狀,改善胰島形態(tài)學(xué)變化。減毒沙門菌作為基因治療載體,在2型糖尿病的基因治療方面,具有巨大的潛在優(yōu)勢。
[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.
【學(xué)位授予單位】:安徽醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R587.1;R450

【參考文獻】

相關(guān)期刊論文 前3條

1 吳冬;劉尚全;袁媛;張維娜;李菲;;不同信號肽對重組胰高血糖素樣肽-1載體表達效率的影響[J];安徽醫(yī)科大學(xué)學(xué)報;2013年07期

2 江中明;殷新民;俞越;繆亮;危薇;周延;殷雪萌;吳瑩瑩;;荷瘤小鼠口服重組減毒鼠傷寒沙門菌后瘤體內(nèi)富集效果的觀察[J];第二軍醫(yī)大學(xué)學(xué)報;2013年04期

3 胡明泰;哈小琴;高鵬;呂同德;惠玲;昌業(yè)偉;唐瑜;;攜帶NK4與IL-2基因真核表達載體的減毒沙門氏菌的構(gòu)建[J];第四軍醫(yī)大學(xué)學(xué)報;2008年08期

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