内脂素基因过表达对大鼠胰岛素敏感性和血浆FGF-21水平的影响

Effects of visfatin gene overexpression on insulin sensitivity and plasma FGF-21 level in rats

目的探讨内脂素基因过表达对大鼠胰岛素敏感性和血浆成纤维细胞生长因子21（FGF-21）的影响。方法构建大鼠内脂素基因重组真核表达质粒，将该质粒转染大鼠。在转染前后采用正糖-高胰岛素钳夹技术评价大鼠胰岛素敏感性变化，并采用放射免疫法测定其血浆FGF-21浓度。结果在质粒注射后3d大鼠血清内脂素水平明显升高（1．49±0．06 vs 0．99±0．04，P〈0．01）；葡萄糖输注率（GIR）[（35．3±1．4 vs 27．6±1．7）mg·kg^-1·min^-1，P〈0．01]较注射前明显升高；基础血浆胰岛素水平明显下降[（14．5±3．7 vs24．4±6．2）mU／L，P〈0．05]；总胆固醇、高密度脂蛋白胆固醇明显降低[（1．31±0．10 vs 1．76±0．22）mmol／L和（0．59±0．04 vs 0．95±0．15）mmol／L，均P〈0．05]；血浆FGF-21也降低[（2．25±0．19 vs 2．59±0．23）μg／L，P〈0．05]；在转染前后基础血糖和血浆脂联素水平无明显变化。结论内脂素质粒转染使大鼠血浆visfatin水平升高和FGF-21水平降低，胰岛素敏感性增强。

Objective To investigate the effects of visfatin gene overexpression on insulin sensitivity and plasma fibroblast growth factor 21 （FGF-21） level in rats. Methods The recombinant visfatin plasmid was constructed and transfected into normal rats. The euglycemic-hyperinsulinemic clamp experiments were performed to evaluate the change of insulin sensitivity before and after administration of the plasmid, and plasma FGF-21 level was determined by radioimmunoassay. Results Plasma visfatin levels and glucose infusion rates （GIR） were significantly increased [ （ 1.49 ± 0.06 vs 0. 99 ± 0.04） and （ 35.3 ± 1.4 vs 27.6 ± 1.7 ） mg·kg^- 1·min^-1, respectively, all P 〈 0.01 ]. Fasting insulin level was significantly decreased [ （ 14.5 ± 3.7 vs 24.4 ± 6.2 ） mU/L, P 〈 0.05 ] , total cholesterol and high-density lipoprotein cholesterol were significantly decreased [ （ 1.31 ± 0.10 vs 1.76 ± 0.22 ） mmol/L and （ 0.59 ± 0.04 vs 0. 95 ± 0.15 ） mmol/L, respectively, all P 〈 0.05 ], and plasma FGF- 21 level was also decreased [ （2.25 ± 0.19 vs 2.59 ± 0.23 ）μg/L, P 〈 0.05 ] after plasmid being injected 3 days compared with that before injection, but there were no significant differences in fasting glucose and adiponectin levels before and after administration. Conclusion The transfection of visfatin plasmid increases plasma visfatin level, decreases FGF-21 levels and improves insulin sensitivity in normal rats.