Metrnl对2型糖尿病小鼠主动脉重构的影响及相关机制研究

Effects of Metrnl on Aortic Remodeling in Type 2 Diabetes Mice and Its Related Mechanisms

目的观察Metrnl在2型糖尿病小鼠中的浓度变化及对小鼠主动脉重构的影响,探讨其可能的作用机制。方法取15只健康雄性小鼠,随机分成对照组(Control组)、糖尿病组(DM组)、Metrnl干预组(DM+Metrnl组),Metrnl干预组予以重组Metrnl,对照组和糖尿病组给予等体积生理盐水。注射结束后测定各组小鼠血脂水平。观察小鼠主动脉病理变化,主动脉内ROS含量,主动脉细胞凋亡情况,主动脉中P-P38 MAPK、P38 MAPK、P-STAT1、STAT1、BAX、BCL-2蛋白表达水平。结果Metrnl干预组体质量及血糖较糖尿病组差异无统计学意义(P>0.05);重组Metrnl干预前,各组小鼠血清Metrnl浓度差异无统计学意义(P>0.05)。Metrnl降低了2型糖尿病小鼠血清TC、TG、LDL-C水平(P<0.05),提高血清HDL-C浓度(P<0.05);Metrnl可改善2型糖尿病小鼠主动脉细胞形态,但无法改变主动脉厚度(P>0.05);Metrnl可减少ROS产生,降低细胞凋亡率(P<0.05),并下调P-P38/P38 MAPK、P-STAT1/STAT1、BAX蛋白表达(P<0.05),提高BCL-2蛋白表达(P<0.05)。结论糖尿病小鼠血清Metrnl水平无明显变化,外源性Metrnl干预不能改善糖尿病小鼠体质量及血糖,但可以改善糖尿病小鼠脂质代谢,Metrnl通过抑制ROS/P38 MAPK/STAT1信号通路,减轻氧化应激损伤,从而发挥对主动脉的保护作用。

Objective To observe the concentration change of Metrnl in type 2 diabetes mice and its effect on aortic remodeling in mice,and explore its possible mechanism.Methods Fifteen healthy male mice were randomly divided into control group(Control group),diabetes group(DM group),and Metrnl intervention group(DM+Metrnl group).The DM+Metrnl group was treated with recombinant Metrnl,while the Control and DM groups were treated with equal volumes of physiological saline.The blood lipid levels of each group of mice after injection were measured.Observation of pathological changes in mouse aorta,ROS content in the aorta,apoptosis of aortic cells,and expression levels of P-P38 MAPK,P38 MAPK,P-STAT1,STAT1,BAX,and BCL-2 proteins in the aorta was carried out.Results There was no significant difference in body mass and blood glucose between the Metrnl intervention group and the diabetes group(P>0.05);Before intervention with recombinant Metrnl,there was no statistically significant difference in serum Metrnl concentration among the groups of mice(P>0.05).Metrnl decreased the levels of serum TC,TG and LDL-C in type 2 diabetes mice(P<0.05),and increased the concentration of serum HDL-C(P<0.05);Metrnl could improve the morphology of aortic cells in type 2 diabetes mice,but could not change the thickness of aorta(P>0.05);Metrnl reduced the production of reactive oxygen species,decreased cell apoptosis rate(P<0.05),and downregulated the expression of P-P38/P38 MAPK,P-STAT1/STAT1 and BAX proteins(P<0.05),while increasing the expression of BCL-2 protein(P<0.05).Conclusion There is no obvious change in the level of serum Metrnl in diabetes mice.Exogenous Metrnl intervention can not improve the body weight and blood sugar of diabetes mice,but can improve the lipid metabolism of diabetes mice.Metrnl plays a protective role in aorta by inhibiting ROS/P38 MAPK/STAT1 signal pathway and alleviating oxidative stress injury.