The effect and mechanism of honokiol regulating mitochondrial apoptosis through the PI3K/AKT signaling pathway on myocardial ischemia/reperfusion injury in mice
Objective To investigate the protective effect and mechanism of honokiol(HK)on the heart of mice with myocardial ischemia/reperfusion injury(MIRI).Methods From June 2022 to July 2023,the experiment was conducted at the Traditional Chinese Medicine Diagnosis Experimental Center of the School of Basic Medicine,Shaanxi University of Chinese Medicine.78 male C57BU6J mice were randomly divided into sham group,MIRI group,and MIRI+HK group,with 26 mice in each group.Before surgery,the MIRI+HK group mice were given HK(02 mg·kg-1·d-1)intraperitoneal injec-tion,while the Sham and MIRI groups were given equal amounts of solvent for 14 consecutive days.The Sham group only threaded without ligation,while the other groups ligated the left anterior descending branch for 30 minutes,then opened the suture and reperfusion for 2 hours to construct a MIRI model.After reperfusion,blood was immediately taken and the heart was stripped.Compare the levels of serum creatine kinase isoenzyme(CK-MB)and cardiac troponin T(cTnT)in each group.Echocardiography detects heart function.Calculate myocardial infarction area using 2,3,5-triphenyl tetrazolium chloride stai-ning method;In situ end labeling technology was used to detect the level of cell apoptosis;Electron microscopy observa-tion of mitochondrial structural damage.Western blot was used to detect mitochondrial apoptosis and protein expression re-lated to the phosphoinositol-3 kinase/protein kinase B(PI3K/AKT)pathway.Results Compared with the Sham group,the MIRI group mice showed higher levels of serum CK-MB,cTnT,left ventricular end systolic diameter(LVESD),myocardial infarction area,and cell apoptosis rate,while the left ventricular ejection fraction(LVEF)and left ventricular short axis short-ening rate(LVFS)decreased(P＜0.001).Most myocardial mitochondria were swollen,with blurred inner and outer bilayers,reduced or absent cristae,and mitochondrial apoptosis related protein cytochrome(Cyto-C)The expression of Bcl-2 related X protein(Bax)and activated cysteine protease(Cleared Caspase-9)increased,while the expression of B lymphocyte tumor 2 gene(Bcl-2),p-AKT/AKT,and p-PI3K/PI3K decreased(P＜0.001).Compared with the MIRI group,the serum CK-MB,cTnT,and LVESD levels,myocardial infarction area,and cell apoptosis rate of the MIRI+HK group mice decreased,while LVEF and LVFS increased(P＜0.001).The mitochondrial ultrastructure of myocardial cells improved and the structure was more complete.The expression of Cyto-C,Bax,and Cleared Caspase-9 proteins decreased,while the expression of Bcl-2,p-AKT/AKT,and p-P13K/PI3K increased(P＜0.001).Conclusion HK can inhibit MIRI induced mitochondrial apoptosis in cardiomyocytes by activating the PI3K/AKT signaling pathway,thereby exerting a cardioprotective effect.
维普
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