Abietic Acid Alleviates the Hypoxic Injury of Cardiomyocytes by Adjusting Autophagy and Apoptosis Mediated by miR-30a-5p/GRP78 Axis.

Abstract

Objective: To explore the influence of abietic acid on the autophagy and apoptosis of cardiomyocytes in rats with acute myocardial infarction (AMI).

Methods: A rat model of AMI was built by ligation of the anterior descending branch of left coronary artery, and a model of hypoxic cardiomyocyte injury was constructed by treating cardiomyocytes with hypoxia. Western blot assay was used to detect the abundance of proteins related to autophagy and apoptosis, MTT assay was used to measure the viability of cardiomyocytes, and the expression level of miR-30a-5p was detected by qRT-PCR. The targeting relationship between miR-30a-5p and GRP78 was determined by double luciferase reporter gene experiment.

Results: After treatment with abietic acid (315mg/kg), the infarct area of AMI rats was noticeably debased, the intensity of cardiomyocyte autophagy was raised and the level of cardiomyocyte apoptosis was decreased. qRT-PCR results showed that abietic acid inhibited the expression of miR-30a-5p. Furthermore, the dual luciferase reporter gene assay demonstrated that miR-30a-5p targets GRP78. It was found that miR-30a-5p mimic could increase the expression of P62, decrease the LC3II/LC3I ratio, promote the expression of BAX, and reduce the expression of anti-apoptotic protein BCL2, while the effect of GRP78 on cardiomyocytes was opposite to that of miR-30a-5p. After the hypoxic myocardial cells were treated with 50 μM abietic acid, the standard of miR-30a-5p decreased and the abundance of GRP78 increased. After the hypoxic myocardial cells were treated with 50 μM abietic acid, the level of miR-30a-5p decreased and the abundance of GRP78 increased.

Conclusion: Abietic acid alleviates the hypoxic injury of cardiomyocytes by adjusting autophagy and apoptosis mediated by miR-30a-5p/GRP78 axis.