Inhibition of miRNA-1-Mediated Inflammation and Autophagy by Astragaloside IV Improves Lipopolysaccharide-Induced Cardiac Dysfunction in Rats

Abstract

Qiuning Wang,1,* Weiying Chen,2,* Xuefeng Yang,3 Ying Song,4 Xiaowei Sun,5 Guizhou Tao,6 Hong Wang,7 Nan Zhao,7 Yue Huang,1 Erqing Chai,8 Futian Tang9 1Department of Pharmacology, Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 2Department of Drug Quality Analysis, Jiuquan Drug Inspection and Testing Center, Jiuquan, Gansu Province, People’s Republic of China; 3Department of Physiology, Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 4Cardiovascular Laboratory, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 5Department of Neurosurgery, China Resources Liaojian Group, General Hospital of Fuxin Mining Group (10th Clinical College of China Medical University), Fuxin, Liaoning Province, People’s Republic of China; 6Internal Medicine-Cardiovascular Department, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 7Allergy and Clinical Immunology Center, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 8Neurointerventional Department, Emergency General Hospital, Beijing, People’s Republic of China; 9Department of Cardiovascular Disease and Key Laboratory of Digestive System Tumor of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Futian Tang, Department of Cardiovascular Disease and Key Laboratory of Digestive System Tumor of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu Province, People’s Republic of China, Email [email protected] Erqing Chai, Neurointerventional Department, Emergency General Hospital, Beijing, People’s Republic of China, Email [email protected]: Astragaloside IV (AS-IV) is one of the main active components isolated from the traditional Chinese medicinal herb, Astragalus membranaceus. The present study was designed to investigate whether the regulation of microRNA-1 (miR-1)-mediated inflammation and autophagy contributes to the protective effect of AS-IV against cardiac dysfunction in rats treated with lipopolysaccharides (LPS).Methods: Animal model of cardiac dysfunction in rats or cellular model of injured H9c2 heart cell line was established by using LPS. Echocardiography, electron microscopy, enzyme-linked immunosorbent assay, immunofluorescence, quantitative RT-PCR, and Western blotting were used to determine the cardiac function and expression of inflammation- and autophagy-related proteins at both the mRNA and protein levels.Results: LPS caused cardiac dysfunction in rats or injury in H9c2 cells and induced inflammation and autophagy. Compared with LPS treatment, AS-IV treatment attenuated cardiac dysfunction or cell injury, accompanied by inhibition of inflammation and autophagy. However, the miR-1 mimics partly abolished the effects of AS-IV. In addition, the effect of the miR-1 inhibitor was similar to that of AS-IV in the LPS model. Further analyses showed that AS-IV treatment decreased the mRNA expression of miR-1 in the heart tissue of rats and H9c2 cells treated with LPS.Conclusion: These results suggest that AS-IV attenuated cardiac dysfunction caused by LPS by inhibiting miR-1-mediated inflammation and autophagy, thereby providing a novel mechanism for the protection against cardiac diseases.Keywords: lipopolysaccharides, astragaloside IV, cardiac dysfunction, inflammation, autophagy, miRNA-1

Keywords

• lipopolysaccharides
• astragaloside iv
• cardiac dysfunction
• inflammation
• autophagy
• mirna-1