期刊
PHARMAZIE
卷 65, 期 10, 页码 760-765出版社
GOVI-VERLAG PHARMAZEUTISCHER VERLAG GMBH
DOI: 10.1691/ph.2010.0576
关键词
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资金
- Heilongjiang Natural Science Foundation [ZJY0707-01]
- Harbin Special Fundation Program for Science and Technology innovative personnel [2010RFXXS050]
- Heilongjiang health department [2009-048]
Objectives: The purpose of this study was to investigate potential roles of rapamycin, a macrocytic lactone produced by Streptomyces hygroscopicus, in myocardial ischemia/reperfusion (I/R) injury. Methods: Male Wistar rats were pretreated with three different doses of rapamycin (0.25, 2, and 5 mg/kg). Then, isolated rat hearts were exposed to 40 min of global ischemia followed by 120 min of reperfusion using a Langendorff apparatus. Western blot analysis was used to examine changes in the expression levels of ERK1/2 and Akt kinases and LC3 -II/I (a marker of autophagy). The area of myocardial infarction and cardiac function were evaluated. Results: Our results demonstrated that rapamycin mediates cardioprotection in a dose-dependent manner in isolated rat hearts during myocardial I/R injury. Significant a autophagy was induced by rapamycin during I/R. Both, the mitochondrial K-ATP-channel blocker 5-hydroxydecanoate (5-HD) and the PI3K inhibitor LY294002 (LY) abolished the protection afforded by rapamycin completely, while the inhibitors alone did not influence the infarct size in control hearts. However, the ERK1/2 inhibitor PD98059(PD) and the blocker of autophagy 3-methyladenine (3-MA) had no effect on rapamycin-mediated cardioprtection. Conclusions: Cardioprotection afforded by rapamycin involves the PI3K pathway and the activation of mitochondrial K-ATP-channels, but is independent of rapamycin-induced autophagy. This study may have significant impact on clinical practice.
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