Protective Effect Of Vasicine Against Myocardial Infarction In Rats Via Modulation Of Oxidative Stress, Inflammation, And The PI3K/Akt Pathway
Authors Jiang T, Zhang L, Ding M, Li M
Received 22 June 2019
Accepted for publication 23 September 2019
Published 31 October 2019 Volume 2019:13 Pages 3773—3784
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 2
Editor who approved publication: Professor Jianbo Sun
Tiechao Jiang,1,2 Lirong Zhang,3 Mei Ding,1,2 Min Li4
1Department of Cardiovascular Medicine, China-Japan Union Hospital of Jilin University, Changchun 130033, People’s Republic of China; 2Jilin Provincial Precision Medicine Key Laboratory for Cardiovascular Genetic Diagnosis, Changchun 130033, People’s Republic of China; 3Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun 130033, People’s Republic of China; 4Department of Clinical Laboratory, China-Japan Union Hospital of Jilin University, Changchun 130033, People’s Republic of China
Correspondence: Mei Ding
Department of Cardiovascular Medicine, China-Japan Union Hospital of Jilin University, 126 Xiantai St, Erdao, Changchun 130033, People’s Republic of China
Tel +86-431-8499 5258
Department of Clinical Laboratory, China-Japan Union Hospital of Jilin University, 126 Xiantai St, Erdao, Changchun 130033, People’s Republic of China
Tel +86-431-8499 5646
Background: Myocardial infarction is the leading cause of damage to the heart and is classified as a major cause of death related to cardiovascular disease. In the present study, we intended to investigate the protective effect of vasicine (VAS) against myocardial infarction in rats, and its mechanism.
Methods: Myocardial infarction was induced by isoproterenol (ISO, 100 mg/kg) at an interval of 24 h for 2 days. Different doses of VAS (2.5, 5, and 10 mg/kg body weight) were administered to the rats. The effect of VAS on oxidative stress markers such as, myocardial necrosis, myocardial ability and infarct volume, inflammatory cytokines, membrane-bound myocardial enzymes, and histopathological changes was investigated. Western blot analysis was also conducted to analyze the effect of VAS on autophagy (PI3K/Akt) and apoptosis (Bcl-2, Bax, and caspase-3). The number of apoptotic cells in the different groups was also identified using TUNEL.
Results: Results suggested that VAS causes reduction in myocardial necrosis by reduction of elevated LDH, CK-MB, and TnT levels. It also causes augmentation of left ventricular systolic pressure (LVSP) and myocardial contractility as determined in terms of +dp/dtmax and –dp/dtmax. Furthermore, VAS causes reduction of TNF-α and IL-6 levels. VAS also improved cardiac function via enhancing posterior wall thickness of the LV with concurrent increase in the mass of LV. In the present study, VAS caused activation of phosphorylated PI3K (p-PI3K) and phosphorylated Akt (p-Akt) in a dose-dependent manner. Furthermore, VAS suppressed apoptosis when tested on animals suffering from ISO-induced MI, by decreasing the expression of cleaved Caspase-3 and Bax while increasing the expression of Bcl-2.
Conclusion: In conclusion, vasicine has a protective effect against MI in vivo, through inhibiting oxidative stress, inflammation and excessive autophagy, to suppress apoptosis via activation of the PI3K/Akt/mTOR signaling pathway.
Keywords: myocardial infarction, vasicine, TNF-α, IL-6, PI3K, Akt, Bcl-2
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