成纤维生长因子21对载脂蛋白E基因敲除小鼠脂质代谢的影响及机制

Effect of FGF21 on lipid metabolism in apoE knockout mice and its mechanism

目的探讨外源性成纤维生长因子21(fibroblast growth factor,FGF21)对载脂蛋白E基因敲除(apoE-/-)小鼠血脂和动脉粥样硬化形成的影响及可能机制。方法雄性apoE-/-小鼠24只,随机分为2组:模型组12只和FGF21组12只,另外12只雄性C57BL/6J小鼠作为对照组。3组均给予高脂饮食8周诱导动脉粥样硬化斑块形成。采血测定血脂,通过HE和油红O染色观察斑块的形态,基因和蛋白表达分别应用实时荧光PCR和Western blot进行检测。结果模型组血管内膜增厚,内膜及中膜均可见巨噬细胞、细胞外脂质沉积及脂质侵蚀。与模型组比较,FGF21组TG[(1.82±0.37)mmol/L vs(2.56±0.39)mmol/L]、TC[(6.27±0.62)mmol/L vs(9.27±0.85)mmol/L]、LDL-C[(2.73±0.26)mmol/L vs(4.37±0.77)mmol/L]明显降低,HDL-C[(1.49±0.25)mmol/L vs(0.99±0.23)mmol/L]、过氧化物酶体增殖物激活受体γmRNA[(4.753±0.648)vs(1.348±0.158)]和FGF受体1mRNA[(145.064±33.203)vs(8.505±11.196)]明显升高(P<0.01)。结论FGF21能降低apoE-/-小鼠血脂及斑块形成,机制可能是通过增加过氧化物酶体增殖物活化受体γ的表达。

Objective To study the effect of exogenous FGF21 on lipid metabolism and atherosclerosis in apoE knockout mice and its mechanism.Methods Twenty-four male apoE knockout mice were randomly divided into model group and FGF21 treatment group（12in each group）.Another12 male C57BL/6Jmice served as a control group.Carotid atherosclerosis was induced in the animals with a high fat diet for 8weeks.Blood samples were taken to test blood lipid.Morphology ofatherosclerotic plaques was observed with HE and oil Red O staining.Gene and protein expressions were detected by RT-PCR and Western blot.Results Typical atherosclerosis was observed in model group,which was characterized by unsmooth aortic intima,fibrosis plaques and infiltration of massive inflammatory cells.The serum levels of TG [（1.82±0.37）mmol/L vs（2.56±0.39）mmol/L],TC[（6.27±0.62）mmol/L vs（9.27±0.85）mmol/L],LDL-C [（2.73±0.26）mmol/L vs（4.37±0.77）mmol/L]were significantly lower whereas those of HDL-C [（1.49±0.25）mmol/L vs（0.99±0.23）mmol/L],PPARγmRNA [（4.753±0.648）vs（1.348±0.158）]and FGFR1mRNA[（145.064±33.203）vs（8.505±11.196）]were significantly higher in FGF21 treatment group than in model group（P〈0.01）.Conclusion FGF21 reduces lipid metabolism and plaque formation in apoE knockout mice by upregulating the expression of PPARγ.