心脑血管病防治2025，Vol.25Issue(12)：7-13,23,后插1,9.DOI:10.3969/j.issn.1009-816x.2025.12.002
乔松素调节LKB1/AMPK/ULK1信号通路对缺血性心肌病大鼠心肌组织线粒体自噬的影响
Effect of pinocembrin on mitophagy in myocardial tissue of rats with ischemic cardiomyopathy via the LKB1/AMPK/ULK1 signaling pathway
摘要
Abstract
Objective To investigate the effect of pinocembrin on mitophagy in myocardial tissue of rats with ischemic cardiomyopathy(ICM)via the regulation of the liver kinase B1(LKB1)/adenosine monophosphate-activated protein kinase(AMPK)/Unc-51-like kinase 1(ULK1)signaling pathway.Methods A total of 36 rats were randomly assigned into six groups:sham control group,model control group,low-dose pinocembrin group,medium-dose pinocembrin group,high-dose pinocembrin group,and AICAR group,with six rats in each group.ICM models were established in the model control,low-dose pinocembrin,medium-dose pinocembrin,high-dose pinocembrin,and AICAR groups by ligating the coronary artery.The sham control group underwent a sham operation involving threading of the coronary artery without ligation.One hour prior to modeling,the low-,medium-,and high-dose pinocembrin groups received intravenous injections of pinocembrin at 2.5 mg/kg,5 mg/kg,and 10 mg/kg,respectively.The AICAR group received a co-administration of pinocembrin(10 mg/kg)and AICAR(100 mg/kg)intravenously.The model control and sham control groups received an equivalent volume of saline.Echocardiography was performed to measure left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in all groups.Serum creatine kinase(CK)and CK-MB levels were determined by enzyme linked immunosorbent assay(ELISA).Histopathological injury in myocardial tissue was assessed by hematoxylin-eosin(HE)staining.Cardiomyocyte apoptosis was determined by TUNEL staining.Mitochondrial ultrastructure was observed by transmission electron microscopy(TEM).The protein expression levels of microtubule-associated protein 1 light chain 3(LC3)Ⅰ,LC3Ⅱ,Beclin-1,P62,LKB1,phosphorylated LKB1(p-LKB1),AMPK,phosphorylated AMPK(p-AMPK),ULK1,and phosphorylated ULK1(p-ULK1)in myocardial tissues were determined via Western blot.Results The levels of LVEF and LVFS were statistically different among the groups(F=103.335,251.842;P<0.05).LVEF and LVFS in the low-,medium-,and high-dose pinocembrin groups significantly increased compared with those in the model control group(P<0.05),while LVEF and LVFS in the AICAR group significantly decreased compared with those in the high-dose pinocembrin group(P<0.05).The levels of serum CK and CK-MB were statistically different among the groups(F=496.539,56.362;P<0.05).Serum levels of CK and CK-MB in the low-,medium-,and high-dose pinocembrin groups significantly decreased compared with those in the model control group(P<0.05),while serum levels of CK and CK-MB in the AICAR group significantly increased compared with those in the high-dose pinocembrin group(P<0.05).Cardiomyocyte structure and morphology in the low-,medium-,and high-dose pinocembrin groups significantly improved compared with those in the model control group.Conversely,the cardiomyocyte structure and morphology in the AICAR group were inferior to those observed in the high-dose pinocembrin group.The myocardial cell apoptosis rate was statistically different among the groups(F=437.433,P<0.05).The cardiomyocyte apoptosis rate in the low-,medium-,and high-dose pinocembrin groups significantly decreased compared with that in the model control group(P<0.05),while the apoptosis rate in the AICAR group significantly increased compared with that in the high-dose pinocembrin group(P<0.05).In the low-,medium-,and high-dose pinocembrin groups,the mitochondrial structure was gradually restored,and the amount of autophagosomes was lower than that in the model control group;while the amount of autophagosomes increased in the AICAR group compared with that in the high-dose pinocembrin group.The protein levels of LC3Ⅱ/LC3Ⅰ,Beclin-1,p-LKB1/LKB1,p-AMPK/AMPK,and p-ULK1/ULK1 decreased,and the protein level of P62 increased in the low-,medium-,and high-dose pinocembrin groups compared with those in the model control group(P<0.05);while the protein levels of LC3Ⅱ/LC3Ⅰ,Beclin-1,p-LKB1/LKB1,p-AMPK/AMPK,and p-ULK1/ULK1 increased,and the protein level of P62 decreased in the AICAR group compared with those in the high-dose pinocembrin group(P<0.05).Conclusion Pinocembrin confers cardioprotective effects in ICM rats by suppressing excessive mitophagy,potentially via the supression of the LKB1/AMPK/ULK1 signaling pathway activation.关键词
乔松素/肝激酶B1/单磷酸腺苷活化蛋白激酶/Unc-51样激酶1信号通路/缺血性心肌病/自噬Key words
Pinocembrin/Liver kinase B1/adenosine monophosphate-activated protein kinase/Unc-51-like kinase 1 signaling pathway/Ischemic cardiomyopathy/Autophagy引用本文复制引用
李召彬,孔佳杰,席树强,柳磊..乔松素调节LKB1/AMPK/ULK1信号通路对缺血性心肌病大鼠心肌组织线粒体自噬的影响[J].心脑血管病防治,2025,25(12):7-13,23,后插1,9.基金项目
河北省医学科学研究课题计划(20241217) （20241217）
