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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 physiological effects of long-term IGF-I and MGF gene therapy on mammalian blood glucose metabolism, an eukaryotic expression vector containing the full-length MGF and IGF-I encoding genes was constructed and then introduced into mice using a live gene delivery system Left quadriceps femoris, a total of 3 times every 2 weeks into the first 15 weeks after the introduction of glucose tolerance test. The long-term sustained expression of IGF-Ⅰcan result in the decrease of glucose metabolism in mice, with the highest value of 12.07 ± 1.35mmol / L being higher than the control (10.15 ± 0.87mmol / L) and the MGF group (10.58 ± 0.61mmol / L ) (P <0.05). MGF alone did not have the above effects on glucose metabolism, but the mice with common IGF-Ⅰ and MGF co-administration had more obvious diminished ability of regulating blood glucose, the highest value ( 16.30 ± 2.69mmol / L) was significantly higher than the other three groups (P <0.001). Therefore, it is speculated that the antagonism of insulin is mainly the N-segment sequence of IGF-I and the IGF-ⅠC sequence which is related to the function of glucose metabolism. Another possibility is that MGF promotes the differentiation of muscle cells to exogenous DNA It can therefore be absorbed and expressed as an adjuvant for gene introduction.