橄榄苦苷通过激活AMPK信号通路缓解小鼠妊娠糖尿病

Oleuropein Alleviates Gestational Diabetes in Mice Partly through Activating AMPK Signaling

目的该研究的目的是探究植物来源的橄榄苦苷对GDM小鼠的作用及相关机制。方法构建GDM小鼠模型,腹腔注射橄榄苦苷(10 mg·kg^(-1)·d^(-1)),记录体质量和血糖水平。通过ELISA和RT-qPCR检测白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和单核细胞趋化蛋白-1(MCP-1)的水平来评估GDM小鼠的炎症水平,通过Western blot检测腺苷酸活化蛋白激酶(AMPK)信号通路的活化,通过比较产仔数和出生体质量来分析妊娠结局。结果橄榄苦苷可以减轻GDM小鼠体质量的升高,并有效降低血糖,恢复胰岛素敏感性。橄榄苦苷治疗还可以降低氧化应激和炎症水平,激活GDM小鼠肝脏组织中的AMPK信号通路,并且橄榄苦苷治疗显著改善了小鼠妊娠结局。结论橄榄苦苷可以有效缓解GDM症状并改善模型小鼠的妊娠结局,这种效果是通过减弱由AMPK信号通路介导的氧化应激和炎症来实现的。

Objective The objective of this study was to investigate the effects and mechanisms of plant-derived oleuropein on GDM mice.Methods Oleuropein was administered to GDM mice at the dose of 10 mg·kg^(-1)·d^(-1).Body weight and blood glucose were recorded.The levels of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein-1(MCP-1)were measured by ELISA and RT-qPCR to assess the inflammation level in GDM mice,the activation of Adenosine 5'-monophosphate-activated protein kinase signaling pathway was measured by Western blot.Gestational outcome was analyzed through comparing litter size and birth weight.Results Oleuropein attenuated the elevated body weight of GDM mice and efficiently reduced blood glucose,and restored insulin sensitivity.Oleuropein treatment also reduced oxidative stress and inflammation levels,activated AMPK signaling pathways in the liver tissues of GDM mice,and significantly improved gestational outcome in mice.Conclusion Oleuropein is effective in alleviating symptoms of GDM and improving gestational outcome in the mouse model.This effect is achieved by attenuating oxidative stress and inflammation,which is mediated by the AMPK signaling pathway.