Anti-apoptotic effects of aspirin following cerebral ischemia-reperfusion injury in rats

BACKGROUND:The pharmacological effects of aspirin on apoptosis are complex.The underlying mechanisms have not been properly defined.OBJECTIVE:To observe the effect of different doses of aspirin on brain cell apoptosis following focal cerebral ischemia-reperfusion injury(CIRI) in rats.DESING,TIME AND SETTING:A randomized,controlled,animal experiment,performed at the School of Medicine and Pharmaceutics,Jiangnan University between June and October 2006.MATERIALS:Twenty-six male,adult,Sprague Dawley rats(grade II),weighing 240-290 g,were obtained from Shanghai Experimental Animal Center,Chinese Academy of Sciences.Aspirin was provided by Sigma(USA).METHODS:The rats were randomly divided into four groups:sham-operation(SO),CIRI + vehicle,CIRI + aspirin(6 mg/kg),and CIRI + aspirin(60 mg/kg).Rats in the lesion groups were intragastrically administrated saline,aspirin(6 mg/kg),or aspirin(60 mg/kg),respectively.MAIN OUTCOME MEASURES:The number of pyramidal neurons with normal appearance in the cerebral cortex at 2-4 mm from the midline;apoptotic cell death as measured by TUNEL;Bcl-2 and Bax protein localization was determined by immunohistochemistry;malondialdehyde(MDA) and super oxidation(SOD) content were determined by biochemistry method;adenosine triphosphate(ATP) content measured by capillary electrophoresis.RESULTS:Following CIRI,the following parameters were altered compared with sham-operated animals:the number of neurons with normal appearance was significantly reduced in the cerebral cortex;the number of apoptotic cells increased;Bax protein expression was enhanced;and the ratio between Bcl-2 and Bax decreased.In addition,MDA content increased significantly,whereas ATP content decreased(P < 0.01).Aspirin ameliorated the loss of healthy pyramidal neurons.Both 6 and 60 mg/kg aspirin increased the ratio between Bcl-2 and Bax,with no significant difference between the treatment groups.In addition,60 mg/kg aspirin decreased MDA content and increased ATP levels.However,6 mg/kg aspirin did not have the same effect.CONCLUSION:Aspirin reduced the number of apoptotic cells following CIRI.These results suggest that the neuroprotective mechanism of aspirin could be related to elevated Bcl-2 protein levels or decreased Bax protein expression.The increase in the ratio of Bcl-2 to Bax appears to be a common anti-apoptotic mechanism of aspirin.