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刺槐碱通过激活ERK1/2/β-连环蛋白信号通路减轻心肌缺血再灌注诱导的心肌损伤。

Aloperine Alleviates Myocardial Injury Induced by Myocardial Ischemia and Reperfusion by Activating the ERK1/2/β-catenin Signaling Pathway.

作者信息

Wei Shichao, Ju Feng, Xiao Junshen, Li Jiaxue, Liu Ting, Hu Zhaoyang

机构信息

Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

Cardiovasc Drugs Ther. 2025 Jun;39(3):533-551. doi: 10.1007/s10557-024-07566-0. Epub 2024 Feb 28.

Abstract

OBJECTIVE

Myocardial ischemia/reperfusion (I/R) injury can cause severe cardiac damage. Aloperine is a quinolizidine alkaloid found in the leaves and seeds of Sophora alopecuroides L. It has been recognized that aloperine has organ-protective properties; however, its role in cardioprotection is poorly characterized. This study aimed to evaluate the cardioprotective effects of aloperine against myocardial I/R injury in vivo.

METHODS

Adult male Sprague‒Dawley rats were randomly divided into sham-operated, control, and aloperine groups. All rats except for the sham-operated rats were subjected to 45 min of myocardial ischemia (by left anterior descending ligation) followed by 3 h of reperfusion. Aloperine (10 mg/kg) was given intravenously at the onset of reperfusion. The cardioprotective effects of aloperine were evaluated by determining infarct size, hemodynamics, histological changes, cardiac biomarkers, and cardiac apoptosis.

RESULTS

Aloperine limited infarct size; improved hemodynamics; attenuated myocardial I/R-induced histological deterioration; decreased serum LDH, CK-MB, and α-HBDH levels; and inhibited apoptosis after myocardial I/R injury. Moreover, aloperine stimulated the phosphorylation of ventricular ERK1/2, which is a major module of MAPK signaling pathways. Furthermore, aloperine increased the ventricular expression levels of β-catenin. Pharmacological inhibition of ERK1/2 diminished aloperine-induced cardioprotection and blocked ERK1/2/β-catenin signaling.

CONCLUSIONS

These data support the cardioprotective effect of aloperine against myocardial I/R injury, which is mediated, at least in part, by the ERK1/2/β-catenin signaling pathway.

摘要

目的

心肌缺血/再灌注(I/R)损伤可导致严重的心脏损害。苦豆碱是一种存在于苦豆子叶片和种子中的喹诺里西啶生物碱。人们已经认识到苦豆碱具有器官保护特性;然而,其在心脏保护中的作用尚未得到充分阐明。本研究旨在评估苦豆碱对体内心肌I/R损伤的心脏保护作用。

方法

成年雄性Sprague-Dawley大鼠随机分为假手术组、对照组和苦豆碱组。除假手术组大鼠外,其余大鼠均通过左前降支结扎进行45分钟的心肌缺血,随后再灌注3小时。在再灌注开始时静脉注射苦豆碱(10mg/kg)。通过测定梗死面积、血流动力学、组织学变化、心脏生物标志物和心脏细胞凋亡来评估苦豆碱的心脏保护作用。

结果

苦豆碱限制了梗死面积;改善了血流动力学;减轻了心肌I/R诱导的组织学恶化;降低了血清乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)和α-羟丁酸脱氢酶(α-HBDH)水平;并抑制了心肌I/R损伤后的细胞凋亡。此外,苦豆碱刺激了心室细胞外信号调节激酶1/2(ERK1/2)的磷酸化,ERK1/2是丝裂原活化蛋白激酶(MAPK)信号通路的主要组成部分。此外,苦豆碱增加了心室β-连环蛋白的表达水平。ERK1/2的药理学抑制减弱了苦豆碱诱导的心脏保护作用,并阻断了ERK1/2/β-连环蛋白信号通路。

结论

这些数据支持苦豆碱对心肌I/R损伤的心脏保护作用,这至少部分是由ERK1/2/β-连环蛋白信号通路介导的。

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