Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury.Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to i...Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury.Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to investigate whether intermittent hypoxia could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. Adult male Sprague-Dawley rats were exposed to hypoxia simulated 5000 m in a hypobaric chamber for 6 h/day, lasting 42 days. Normoxia group rats were kept under normoxic conditions. Isolated perfused hearts from both groups were subjected to 30 min of global ischemia followed by 60 min reperfusion.Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA agarose gel electrophoresis. Expressions of apoptosis related proteins,Bax and Bcl-2, in cytosolic and membrane fraction were detected by Western Blotting. After ischemia/reperfusion,enhanced recovery of cardiac function was observed in intermittent hypoxia hearts compared with normoxia group.Ischemia/reperfusion-induced apoptosis, as evidenced by TUNEL-positive nuclei and DNA fragmentation, was significantly reduced in intermittent hypoxia group compared with normoxia group. After ischemia/reperfusion,expression of Bax in both cytosolic and membrane fractions was decreased in intermittent hypoxia hearts compared with normoxia group. Although ischemia/reperfusion did not induce changes in the level of Bcl-2 expression in cytosolic fraction between intermittent hypoxia and normoxia groups, the expression of Bcl-2 in membrane fraction was upregulated in intermittent hypoxia group compared with normoxia group. These results indicated that the cardioprotection of intermittent hypoxia against ischemia/reperfusion injury appears to be in part due to reduce myocardial apoptosis. Intermittent hypoxia attenuated ischemia/reperfusion-induced apoptosis via increasing the ratio of Bcl-2/Bax, especially in membrane fraction.展开更多
Objective:Cardiac hypertrophy is an adaptive reaction of the heart against cardiac overloading,but continuous cardiac hypertrophy can lead to cardiac remodeling and heart failure.Cardiac hypertrophy is mostly consider...Objective:Cardiac hypertrophy is an adaptive reaction of the heart against cardiac overloading,but continuous cardiac hypertrophy can lead to cardiac remodeling and heart failure.Cardiac hypertrophy is mostly considered reversible,and recent studies have indicated that decorin not only prevents cardiac fibrosis associated with hypertension,but also achieves therapeutic effects by blocking fibrosis-related signaling pathways.However,the mechanism of action of decorin remains unknown and unconfirmed.Methods:We determined the degree of myocardial hypertrophy by measuring the ratios of the heart weight/body weight and left ventricular weight/body weight,histological analysis and immunohistochemistry.Western blotting was performed to detect the expression levels of CaMKⅡ,p-CaMKⅡ and MEF-2 in the heart.Results:Our results confirmed that decorin can regulate the CaMKⅡ/MEF-2 signaling pathway,with inhibition thereof being similar to that of decorin in reducing cardiac hypertrophy.Conclusion:Taken together,the results of the present study showed that decorin induced cardiac hypertrophy by regulating the CaMKⅡ/MEF-2 signaling pathway in vivo,revealing a new therapeutic approach for the prevention of cardiac hypertrophy.展开更多
基金The study was supported by grants from National Natural Science Foundation of Chinathe Science and Technology committee of Shanghai Municipality(02JC14038).
文摘Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury.Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to investigate whether intermittent hypoxia could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. Adult male Sprague-Dawley rats were exposed to hypoxia simulated 5000 m in a hypobaric chamber for 6 h/day, lasting 42 days. Normoxia group rats were kept under normoxic conditions. Isolated perfused hearts from both groups were subjected to 30 min of global ischemia followed by 60 min reperfusion.Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA agarose gel electrophoresis. Expressions of apoptosis related proteins,Bax and Bcl-2, in cytosolic and membrane fraction were detected by Western Blotting. After ischemia/reperfusion,enhanced recovery of cardiac function was observed in intermittent hypoxia hearts compared with normoxia group.Ischemia/reperfusion-induced apoptosis, as evidenced by TUNEL-positive nuclei and DNA fragmentation, was significantly reduced in intermittent hypoxia group compared with normoxia group. After ischemia/reperfusion,expression of Bax in both cytosolic and membrane fractions was decreased in intermittent hypoxia hearts compared with normoxia group. Although ischemia/reperfusion did not induce changes in the level of Bcl-2 expression in cytosolic fraction between intermittent hypoxia and normoxia groups, the expression of Bcl-2 in membrane fraction was upregulated in intermittent hypoxia group compared with normoxia group. These results indicated that the cardioprotection of intermittent hypoxia against ischemia/reperfusion injury appears to be in part due to reduce myocardial apoptosis. Intermittent hypoxia attenuated ischemia/reperfusion-induced apoptosis via increasing the ratio of Bcl-2/Bax, especially in membrane fraction.
文摘Objective:Cardiac hypertrophy is an adaptive reaction of the heart against cardiac overloading,but continuous cardiac hypertrophy can lead to cardiac remodeling and heart failure.Cardiac hypertrophy is mostly considered reversible,and recent studies have indicated that decorin not only prevents cardiac fibrosis associated with hypertension,but also achieves therapeutic effects by blocking fibrosis-related signaling pathways.However,the mechanism of action of decorin remains unknown and unconfirmed.Methods:We determined the degree of myocardial hypertrophy by measuring the ratios of the heart weight/body weight and left ventricular weight/body weight,histological analysis and immunohistochemistry.Western blotting was performed to detect the expression levels of CaMKⅡ,p-CaMKⅡ and MEF-2 in the heart.Results:Our results confirmed that decorin can regulate the CaMKⅡ/MEF-2 signaling pathway,with inhibition thereof being similar to that of decorin in reducing cardiac hypertrophy.Conclusion:Taken together,the results of the present study showed that decorin induced cardiac hypertrophy by regulating the CaMKⅡ/MEF-2 signaling pathway in vivo,revealing a new therapeutic approach for the prevention of cardiac hypertrophy.
