Myocardial infarction (MI) is associated with a high risk of mortality and is a major global health concern. The present study aimed to investigate the protective effects of (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one (TIM) against MI induced by isoproterenol (ISO) in a rat model and the underlying mechanisms. Wistar rats were assigned to 4 groups (n=10): The control group received saline treatment; the ISO group received an intraperitoneal injection of ISO (100 mg/kg); and the TIM (low) and TIM (high) groups received an intraperitoneal injection of ISO, plus a 1 and 2 mg/kg dose of TIM orally, respectively. TIM rats were treated with TIM daily for 12 days and received ISO injections on the final 2 days to induce MI. Cardiac function, apoptosis index and protein expression were subsequently determined. The levels of oxidative stress markers were determined by ELISAs, whereas DNA damage was detected using a Cell Death Detection ELISA kit. Gene and protein expression were determined via reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. Following treatment with ISO, the maximum left ventricular contraction/relaxation velocity and left ventricular systolic pressure were significantly decreased, whereas the left ventricular end-diastolic pressure was increased; however, treatment with TIM significantly ameliorated ISO-induced cardiac dysfunction. Additionally, TIM treatment significantly decreased oxidative stress and inhibited the apoptosis of cardiomyocytes, as determined by a decrease in caspase activities, increased expression of B-cell lymphoma 2 (Bcl-2) and reduced expression of cleaved caspase-3, cleaved caspase-9 and Bcl-2-associated X. Furthermore, treatment with TIM upregulated the levels of apelin in the plasma and myocardium of ISO-treated rats. The results indicated that TIM protected cardiomyocytes against ISO-induced MI, potentially via the apelin/apelin receptor signaling pathway. The results of the present study suggested that TIM may be a potential novel therapy for the treatment of MI.
[1]Jilin Univ, China Japan Union Hosp, Dept Cardiol, 126 Xiantai St, Changchun 130033, Jilin, Peoples R China.
[2]Jilin Univ, China Japan Union Hosp, Dept Hepatobiliary Pancreat Surg, Changchun 130033, Jilin, Peoples R China.
[3]Jilin Univ, China Japan Union Hosp, Dept Emergency, 126 Xiantai St, Changchun 130033, Jilin, Peoples R China.
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