Research Article: Astragaloside IV alleviates myocardial ischemia-reperfusion injury in rats through regulating PI3K/AKT/GSK-3β signaling pathways1

Date Published: September 12, 2019

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia

Author(s): Dajun Wei, Hongjie Xu, Xiaodong Gai, Ying Jiang.

http://doi.org/10.1590/s0102-865020190070000008

Abstract

To investigate the effect of astragaloside IV (As-IV) on myocardial ischemia-reperfusion (I/R) injury in rats and reltaed mechanisms.

Sixty rats were randomly divided into sham-operated, control I/R and 2.5, 5 and 10 mg/kg As-IV groups, 12 rats in each group. The later three groups were intragastrically administered with As-IV for 7 days, with a dose of 2.5, 5 and 10 mg/kg, respectively. The myocardial I/R injury model was constructed in later four groups. At the end of reperfusion, the cardiac function indexes, serum lactate dehydrogenase (LDH) and creatine kinase (CK) levels, heart weight (HW)/body weight (BW) ratio and infarct size, and expressions of phosphatidylinositol-3 kinase/serine-threonine protein kinase (PI3K/AKT) and glycogen synthase kinase-3β (GSK-3β) proteins and the phosphorylated forms (p-AKT, p-GSK-3β) were determined.

Compared with control I/R group, in 5 and 10 mg/kg As-IV groups the left ventricular systolic pressure, fractional shortening and ejection fraction were increased, the left ventricular end-diastolic pressure was decreased, the serum LDH and CK levels were decreased, the HW/BW ratio and myocardial infarct size were decreased, and the p-Akt/Akt ratio and p-GSK-3β/GSK-3β ratio were increased (all P < 0.05). As-IV can alleviate the myocardial I/R injury in rats through regulating PI3K/AKT/GSK-3β signaling pathways.

Partial Text

Myocardial ischemia-reperfusion (I/R) injury is the lesion in which the blood perfusion is restored after the myocardial blood supply is interrupted for a certain period, leading to the injury or dysfunction in ischemic area1. Myocardial I/R injury can lead to the impairment of cardiac function and damage of myocardial cells, which increases the risk of cardiovascular events, such as myocardial infarction and arrhythmia, and seriously affects the prognosis of underlying diseases2,3. In addition, the myocardial I/R injury can limit the application of coronary thrombolysis treatment, interventional therapy and bypass surgery4. Therefore, reducing myocardial I/R injury is of great significance to improve the curative effect of cardiovascular diseases. Astragaloside IV (As-IV) is one of the important effective chemical constituents of Astragalus membranaceus, a widely used Chinese herbal medicine (Fig. 1).

This study was approved by the ethics committee of the Affiliated Hospital of Beihua University. All animal procedures followed the Principles of Laboratory Animal Care and were in accordance with the Guide for the Care and Use of Laboratory Animals by the National Institutes of Health.

Restoration of reperfusion after myocardial ischemia within a certain period of time may be accompanied by I/R injury. The etiology of myocardial I/R injury is not yet clear, but it can reduce the cardiac function and increase myocardial cell damage19. Myocardial I/R injury is the main problem hindering the ischemic myocardium benefiting from therapy with reperfusion. Astragalus membranaceus is a widely used traditional Chinese medicine for the treatment of various heart diseases. It can improve the cardiac function and reduce cardiac myocyte apoptosis20. As-IV, the main active ingredient of Astragalus membranaceus, has a variety of biological activities, such as alleviating apoptosis of neurons around cerebral hemorrhage focus21 and attenuating myocardial infarction22, suggesting that it has a good cardiovascular protective effect. This study constructed the myocardial I/R injury model of rats and investigated the protective effect of As-IV. Result showed that, compared with control I/R group, in 5 mg/kg As-IV and 10 mg/kg As-IV groups, the LVSP, FS and EF were significantly increased, the LVEDP was significantly decreased, the serum LDH and CK levels were significantly decreased, and the HW/BW ratio and myocardial infarct size were significantly decreased. This indicates that, As-IV can alleviate the myocardial I/R injury in rats.

As-IV can alleviate the myocardial I/R injury in rats. The possible mechanism is related to it increasing phosphorylation of PI3K/AKT and GSK-3β protein and activating PI3K/AKT/GSK-3β signaling pathway. This study has provided a basis for further clarifying the mechanism for the protective effect of As-IV on myocardial I/R injury. In the next study, the upstream and downstream pathways of PI3K/AKT/GSK-3β signal pathways will be further studied to provide more abundant theoretical basis for clinical application of As-IV to prevention and treatment of myocardial I/R injury.

 

Source:

http://doi.org/10.1590/s0102-865020190070000008

 

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