Sodium tanshinone IIA sulfonate protects rat myocardium against ischemia-reperfusion injury via activation of PI3K/Akt/FOXO3A/Bim pathway
| Autor: | Jian-hong Lu, Ye Shen, Shu-ren Yuan, Xiang-hong Yang, Meiqi Zhang, Jing-jie Chai, Jian-feng Tu, Jun-ping Guo, Liang-zhong Chen, Yue-liang Zheng, Chang-lin Zhai, Huan Chen |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Cardiotonic Agents Morpholines Myocardial Infarction Ischemia Apoptosis Myocardial Reperfusion Injury Pharmacology Rats Sprague-Dawley Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins In Situ Nick-End Labeling medicine Animals Myocytes Cardiac Pharmacology (medical) cardiovascular diseases Protein kinase B PI3K/AKT/mTOR pathway Bcl-2-Like Protein 11 Traditional medicine business.industry Forkhead Box Protein O3 Membrane Proteins Forkhead Transcription Factors General Medicine Phenanthrenes Flow Cytometry medicine.disease Rats Disease Models Animal Animals Newborn Gene Expression Regulation Chromones Sodium tanshinone IIA sulfonate Original Article Rat myocardium Apoptosis Regulatory Proteins business Proto-Oncogene Proteins c-akt Reperfusion injury Signal Transduction |
| Zdroj: | Acta Pharmacologica Sinica. 34:1386-1396 |
| ISSN: | 1745-7254 1671-4083 |
| Popis: | To investigate the mechanisms underlying the protective effects of sodium tanshinone IIA sulfonate (STS) in an ischemia-reperfusion (I/R)-induced rat myocardial injury model.Male SD rats were iv injected with STS, STS+LY294002 or saline (NS) for 15 d. Then the hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion. Cardiac function, infarction size and area at risk were assessed. Cell apoptosis was evaluated with TUNEL staining, DNA laddering and measuring caspase-3 activity. In addition, isolated cardiomyocytes of neonatal rats were pretreated with the above drugs, then exposed to H2O2 (200 mol/L) for 1 h. Cell apoptosis was detected using flow cytometric assay. The levels of p-Akt, p-FOXO3A and Bim were examined with immunoblotting.Compared to NS group, administration of STS (20 mg/kg) significantly reduced myocardial infarct size (40.28%±5.36% in STS group vs 59.52%±7.28% in NS group), and improved the myocardial function as demonstrated by the increased values of dp/dtmax, LVDP and coronary flow at different reperfusion time stages. Furthermore, STS significantly decreased the rate of apoptotic cells (15.11%±3.71% in STS group vs 38.21%±7.83% in NS group), and reduced caspase-3 activity to nearly a quarter of that in NS group. Moreover, STS significantly increased the phosphorylation of Akt and its downstream target FOXO3A, and decreased the expression of pro-apoptotic gene Bim. Co-treatment with the PI3K inhibitor LY294002 (40 mg/kg) partially countered the protective effects induced by STS treatment. In isolated cardiomyocytes, STS exerted similar protective effects as shown in the ex vivo I/R model.STS pretreatment reduces infarct size and improves cardiac function in an I/R-induced rat myocardial injury model via activation of Akt/FOXO3A/Bim-mediated signal pathway. |
| Databáze: | OpenAIRE |
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