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 apo...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 iscbemia-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 24 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.展开更多
文摘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 iscbemia-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 24 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.
