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作 者:李闯 马晓莉[1,2] 文志萍 陈卫军[1,2] 袁勇 王新春[1,2] 曹文疆[2] LI Chuang;MA Xiao-li;WEN Zhi-ping;CHEN Wei-jun;YUAN Yong;WANG Xin-chun;CAO Wen-jiang(College of Pharmacy,Shihezi University,Shihezi 832002,China;The First Hospital Affiliated to College of Medicine,Shihezi University,Shihezi 832008,China)
机构地区:[1]石河子大学药学院,新疆石河子832002 [2]石河子大学医学院第一附属医院,新疆石河子832008
出 处:《中成药》2022年第2期390-395,共6页Chinese Traditional Patent Medicine
基 金:国家自然科学基金资助项目(81860747,81960766)。
摘 要:目的研究香青兰总黄酮对心肌缺血再灌注损伤(MIRI)过程中氧化应激和线粒体损伤的影响。方法结扎大鼠冠状动脉左前降支缺血30 min,再灌注灌2 h构建MIRI模型。SD大鼠随机分为假手术组、模型组、香青兰总黄酮组、香青兰总黄酮+AMPK抑制剂Compound C组、香青兰总黄酮+SIRT1抑制剂EX-527组,每组10只。TTC染色法检测心肌梗死面积,检测ROS、MDA水平及SOD活性反映抗氧化能力,免疫组化法检测AMPK、SIRT1及PGC-1α蛋白表达,透射电镜检测线粒体超微结构。结果与模型组比较,香青兰总黄酮可以减轻大鼠心肌梗死面积(P<0.01),降低ROS和MDA水平(P<0.01),增加SOD活性(P<0.01),上调AMPK、SIRT1和PGC-1α蛋白表达(P<0.05,P<0.01),改善线粒体的超微结构损伤;与香青兰总黄酮组比较,香青兰总黄酮+Compound C组和香青兰总黄酮+EX-527组大鼠上述指标的改善作用均被逆转(P<0.05,P<0.01)。结论香青兰总黄酮具有保护心肌缺血再灌注损伤的作用,其机制可能与AMPK/SIRT1/PGC-1α信号转导通路的激活有关。AIM To study the effects of Dracocephalum moldavica L.total flavonoids on oxidative stress and mitochondrial damage during myocardial ischemia-reperfusion injury(MIRI).METHODS The MIRI rat models were established by 2 hours of reperfusion following 30 min coronary occlusion.SD rats were randomly divided into sham group,model group,D.moldavica total flavonoids group,the group for use of D.moldavica total flavonoids and AMPK inhibitor Compound C,and the group for use of D.moldavica total flavonoids and SIRT1 inhibitor EX-527,with 10 rats in each group.The rats were subsequently subjected to the determination of myocardial infarction area by TTC staining;the measurement of antioxidant capacity in terms of ROS and MDA levels,and SOD activity;the investigation of the protein expressions of AMPK,SIRT1 and PGC-1α by immunohistochemistry,and the mitochondrial ultrastructure by transmission electron microscopy.RESULTS Compared with the model group,the group intervened solely with D.moldavica total flavonoids shared reduced myocardial infarction area(P<0.01) and ROS and MDA levels(P<0.01),increased SOD activity(P<0.01),increased protein expressions of AMPK,SIRT1 and PGC-1α(P<0.05,P<0.01),and improved mitochondrial ultrastructure damage.Compared with D.moldavica total flavonoids group,the groups given combinative administration with either Compound C or EX-527 displayed inferiority in terms of the aforementioned indices levels(P<0.05,P<0.01).CONCLUSION Being an MIRI inhibitor,D.moldavica total flavonoids may activate AMPK/SIRT1/PGC-1α signal transduction pathway.
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