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机构地区:[1]北京科技大学生物工程与传感技术研究中心,北京100083 [2]北京科技大学化学与生物工程学院生物技术系,北京100083
出 处:《中国生物工程杂志》2012年第4期7-11,共5页China Biotechnology
基 金:国家自然科学基金(30800540)资助项目
摘 要:为研究IGF-Ⅰ和MGF长期基因治疗对哺乳动物血糖代谢的生理影响,首先构建了包含MGF和IGF-Ⅰ全长编码基因的真核表达载体,然后使用活体基因导入仪将其导入小鼠的左侧股四头肌,每2周一次共导入3次,首次导入15周后进行糖耐量测定实验。实验证实IGF-Ⅰ的长期持续表达会导致小鼠的糖代谢能力降低,血糖最高值可达到12.07±1.35mmol/L比对照(10.15±0.87mmol/L)和MGF组(10.58±0.61mmol/L)有显著性的升高(P<0.05),MGF单独存在情况下在糖代谢方面则没有上述作用,但是IGF-Ⅰ和MGF共同导入的小鼠的血糖调节能力更明显减弱,其最高值(16.30±2.69mmol/L)明显高于其它3组(P<0.001)。因此推测与胰岛素进行拮抗作用的主要是IGF-Ⅰ的N段序列,而产生与糖代谢相关功能的则为暴露的IGF-ⅠC段序列;另一种可能是MGF促进了肌肉细胞对外源DNA的吸收和表达因此其可以作为基因导入的佐剂。To investigate the long term effect of glucose metabolism in gene therapy by using IGF-Ⅰ and MGF,the MGF and IGF-Ⅰ eukaryotic expression vector were constructed,and then imported into the left quadriceps of mice every 2 weeks.The sugar tolerance of these mice was tested at the 15th week after the first injection by Yicheng blood glucose meter(JPS-5).It was found that the balance of glucose tolerance was broken when IGF-Ⅰ gene were injected into mice,the blood glucose could reach 12.07 ± 1.35mmol / L,which is significantly higher than the control group(10.15±0.87mmol/L) and the MGF group(10.58 ± 0.61mmol/L).At the same time,the combine injection of both MGF and IGF-Ⅰcould significant reduce the ability of regulating blood sugar,the value(16.30 ± 2.69mmol / L) was rank highest in all of the tested group(P 0.001).Long-term presence of IGF-Ⅰ may antagonize insulin in vivo and then reduce the ability of glycometabolism,however,MGF does not show this function.Integrating the results of combination with IGF-Ⅰand MGF,the speculation that IGF-Ⅰantagonize to insulin mainly through its N-terminal,and its C-terminal which exposed do the formation and function of glucose metabolism could be made,or MGF promotes muscle cell to absorb and express exogenous DNA,which can be used as an adjuvant of gene vaccine.
关 键 词:胰岛素样生长因子-Ⅰ 机械生长因子 血糖代谢
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