Leonurine pretreatment protects the heart from myocardial ischemia-reperfusion injury

被引:8
作者
Lu, Huiping [1 ,2 ]
Gong, Jingru [1 ,2 ]
Zhang, Tongtong [1 ,2 ]
Jiang, Zhe [1 ,2 ]
Dong, Wenmin [1 ,2 ]
Dai, Jing [3 ]
Ma, Fenfen [1 ,2 ]
机构
[1] Fudan Univ, Shanghai Pudong Hosp, Dept Pharm, Pudong Med Ctr, Shanghai 201399, Peoples R China
[2] Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
[3] Hebei Med Univ, Dept Clin Diagnost, Shijiazhuang 050017, Peoples R China
关键词
Leonurine; ischemia-reperfusion injury; cardioprotective; apoptosis; anti-oxidation; GROWTH-FACTOR; STRESS; RAT;
D O I
10.1177/15353702231198066
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Myocardial ischemia-reperfusion (I/R), an important complication of reperfusion therapy for myocardial infarction, is characterized by hyperactive oxidative stress and inflammatory response. Leonurine (4-guanidino-n-butyl syringate, SCM-198), an alkaloid extracted from Herbaleonuri, was previously found to be highly cardioprotective both in vitro and in vivo. Our current study aimed to investigate the effect of SCM-198 preconditioning on myocardial I/R injury in vitro and in vivo, respectively, as well as to decipher the mechanism involved. Rats were pretreated with SCM-198 before subjected to 45 min of myocardial ischemia, which was followed by 24 h of reperfusion. Primary neonatal rat cardiac ventricular myocytes (NRCMs) were exposed to hypoxia (95% N2 + 5% CO2) for 12 h, and then to 12 h reoxygenation so as to mimic I/R. The enzymatic measurements demonstrated that SCM-198 reduced the release of infarction-related enzymes, and the hemodynamic and echocardiography measurements showed that SCM-198 restored cardiac functions, which suggested that SCM-198 could significantly reduce infarct size, maintaining cardiomyocyte morphology, and that SCM-198 pretreatment could significantly reduce cardiomyocytes apoptosis. Moreover, we demonstrated that SCM-198 could exert a cardioprotective effect by reducing reactive oxygen species (ROS) level and Akt phosphorylation while reducing the phosphorylation of p38 and JNK. In addition, the upregulation of p-Akt, Bcl-2/Bax induced by SCM-198 treatment were blocked by PI3K inhibitor LY294002, and the total protein level of Akt was not affected by SCM-198 pretreatment. Our experimental results indicated that SCM-198 could have a cardioprotective effect on I/R injury, which confirmed the utility of SCM-198 preconditioning as a strategy to prevent I/R injury.
引用
收藏
页码:1566 / 1578
页数:13
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