Atorvastatin Inhibits Fas Expression in Ischemia-Reperfusion Induced Myocardial Cell Injury
Abstract
BACKGROUND: Atorvastatin has been shown to be cardioprotective in ischemia-reperfusion (I/R) injury. Inhibition of Fas expression prevents I/R induced apoptosis. However, the influence of atorvastatin on Fas expression in I/R injury was not studied. Therefore, we designed this study to see the influence of atorvastatin on cardiomyocyte apoptosis and Fas expression following acute I/R in vivo.
METHODS: Thirty Wistar rats were selected and divided into three groups (n = 10): acute ischemia-reperfusion (I/R) group, acute ischemia-reperfusion and treated with atorvastatin group and sham-operated group. Apoptosis of the cardiomyocytes was observed under electron microscopy and determined by optic microscopy with TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling) staining. To detect the expression of Fas in the cardiomyocytes, immunohistochemistry method was used. Image analysis system was used to quantitatively estimate the positive metric substances of immunohistochemistry through the mean optic density.
RESULTS: Numerous apoptotic cardiomyocytes were found in ischemic fields in ischemia-reperfusion groups and weren’t observed in the sham-operated group. Fas expression was significantly higher in the ischemia-reperfusion group as compared to sham-operated group, but was decreased significantly in atorvastatin treated group as compared with I/R group.
CONCLUSION: Upregulation of Fas expression in myocardial ischemia-reperfusion can induce cardiomyocyte apoptosis,
and atorvastatin can significantly inhibit cardiomyocyte apoptosis by inhibiting Fas expression.
KEY WORDS: Fas, atorvastatin, ischemia-reperfusion, apoptosis.
METHODS: Thirty Wistar rats were selected and divided into three groups (n = 10): acute ischemia-reperfusion (I/R) group, acute ischemia-reperfusion and treated with atorvastatin group and sham-operated group. Apoptosis of the cardiomyocytes was observed under electron microscopy and determined by optic microscopy with TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling) staining. To detect the expression of Fas in the cardiomyocytes, immunohistochemistry method was used. Image analysis system was used to quantitatively estimate the positive metric substances of immunohistochemistry through the mean optic density.
RESULTS: Numerous apoptotic cardiomyocytes were found in ischemic fields in ischemia-reperfusion groups and weren’t observed in the sham-operated group. Fas expression was significantly higher in the ischemia-reperfusion group as compared to sham-operated group, but was decreased significantly in atorvastatin treated group as compared with I/R group.
CONCLUSION: Upregulation of Fas expression in myocardial ischemia-reperfusion can induce cardiomyocyte apoptosis,
and atorvastatin can significantly inhibit cardiomyocyte apoptosis by inhibiting Fas expression.
KEY WORDS: Fas, atorvastatin, ischemia-reperfusion, apoptosis.