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Puerarin pretreatment attenuates cardiomyocyte apoptosis induced by coronary microembolization in rats by activating the PI3K/Akt/GSK-3β signaling pathway

Korean Journal of Physiology & Pharmacology 2021년 25권 2호 p.147 ~ 157
Chen Zhi-Qing, Zhou You, Huang Jun-Wen, Chen Feng, Zheng Jing, Li Hao-Liang, Li Tao, Li Lang,
소속 상세정보
 ( Chen Zhi-Qing ) - Guangxi Medical University First Affiliated Hospital Department of Cardiology
 ( Zhou You ) - Guangxi Medical University First Affiliated Hospital Department of Cardiology
 ( Huang Jun-Wen ) - Guangxi Medical University First Affiliated Hospital Department of Cardiology
 ( Chen Feng ) - Guangxi Medical University First Affiliated Hospital Department of Emergency
 ( Zheng Jing ) - Guangxi Medical University First Affiliated Hospital Department of Cardiology
 ( Li Hao-Liang ) - Guangxi Medical University First Affiliated Hospital Department of Cardiology
 ( Li Tao ) - Guangxi Medical University First Affiliated Hospital Department of Cardiology
 ( Li Lang ) - Guangxi Medical University First Affiliated Hospital Department of Cardiology

Abstract


Coronary microembolization (CME) is associated with cardiomyocyte apoptosis and cardiac dysfunction. Puerarin confers protection against multiple cardiovascular diseases, but its effects and specific mechanisms on CME are not fully known. Hence, our study investigated whether puerarin pretreatment could alleviate cardiomyocyte apoptosis and improve cardiac function following CME. The molecular mechanism associated was also explored. A total of 48 Sprague-Dawley rats were randomly divided into CME, CME + Puerarin (CME + Pue), sham, and sham + Puerarin (sham + Pue) groups (with 12 rats per group). A CME model was established in CME and CME + Pue groups by injecting 42 μm microspheres into the left ventricle of rats. Rats in the CME + Pue and sham + Pue groups were intraperitoneally injected with puerarin at 120 mg/kg daily for 7 days before operation. Cardiac function, myocardial histopathology, and cardiomyocyte apoptosis index were determined via cardiac ultrasound, hematoxylin-eosin (H&E) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Western blotting was used to measure protein expression related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. We found that, puerarin significantly ameliorated cardiac dysfunction after CME, attenuated myocardial infarct size, and reduced myocardial apoptotic index. Besides, puerarin inhibited cardiomyocyte apoptosis, as revealed by decreased Bax and cleaved caspase-3, and up-regulated Bcl-2 and PI3K/Akt/GSK-3β pathway related proteins. Collectively, puerarin can inhibit cardiomyocyte apoptosis and thus attenuate myocardial injury caused by CME. Mechanistically, these effects may be achieved through activation of the PI3K/Akt/GSK-3β pathway.

키워드

Apoptosis; Coronary microembolization; Myocardial injury; PI3K/Akt/GSK-3; Puerarin

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