灯盏花素调控Nrf2/Gpx4通路对MIRI模型心肌凋亡的影响及作用机制研究

Breviscapine regulates the effect of Nrf2/Gpx4 pathway on myocardial apoptosis in MIRI model and its mechanism

[目的]探究灯盏花素调控核因子E2相关因子2(Nrf2)/谷胱甘肽过氧化物酶4(Gpx4)通路对心肌缺血再灌注损伤(MIRI)模型心肌凋亡的影响及作用机制。[方法]45只大鼠随机分为Sham组、MIRI组和MIRI+灯盏花素组,每组15只。通过结扎左前降支冠状动脉建立MIRI模型,建模24 h后,MIRI+灯盏花素组使用灯盏花素灌胃(200 mg/kg,1次/d,7 d)。比较各组大鼠心功能、心肌组织损伤、细胞凋亡、血清氧化应激因子、Nrf2/Gpx4通路表达水平。[结果]3组的上述指标比较差异显著(P<0.05)。MIRI组的左室收缩压力(LVESP)、上升和下降速率(±dP/dt max)、超氧化物歧化酶(SOD)、Nrf2和Gpx4 mRNA和蛋白水平显著低于Sham组,左室舒张末压力(LVEDP)、凋亡指数、丙二醛(MDA)水平显著高于Sham组(P<0.05)。MIRI+灯盏花素组的LVESP、±dP/dt max、SOD、Nrf2和Gpx4 mRNA和蛋白水平显著高于MIRI组,而LVEDP、凋亡指数和MDA显著低于MIRI组(P<0.05)。[结论]灯盏花素具有缓解MIRI模型大鼠心肌细胞凋亡的功能,并且其保护心功能的机制可能与促进Nrf2/Gpx4通路有关。

[Objective]To explore the effect and mechanism of breviscapine’s regulation of nuclear factor E2-related factor 2(Nrf2)/glutathione peroxidase 4(Gpx4)pathway on myocardial apoptosis in myocardial ischemia reperfusion injury(MIRI)models.[Methods]The 45 rats were randomly divided into Sham group,MIRI group and MIRI+breviscapine group(n=15).The MIRI model was established by ligating the left anterior descending coronary artery.After 24 h of modeling,the MIRI+breviscapine group was given breviscapine by gavage(200 mg/kg,1 time/d,7 d).Cardiac function,myocardial tissue injury,apoptosis,serum oxidative stress factor,and Nrf2/Gpx4 pathway expression levels were compared in each group.[Results]The above indicators of the three groups were significantly different(P<0.05).LVESP,±dP/dt max,SOD,Nrf2 and Gpx4 mRNA in MIRI group.And protein levels were significantly lower than those in Sham group,LVEDP,apoptosis index,MDA levels were significantly higher than thosein Sham group(P<0.05).LVESP,±dP/dt max,SOD,Nrf2 and Gpx4 mRNA and protein levels in MIRI+breviscapine group were significantly higher than those in MIRI group,while LVEDP,apoptosis index and MDA were significantly lower than those in MIRI group(P<0.05).[Conclusion]Breviscapine has the function of alleviating myocardial cell apoptosis in MIRI model rats,and its mechanism of protecting heart function may be related to the promotion of Nrf2/Gpx4 pathway.