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

作者：Qiu Liying^*; Du Bin; Li Ying; Fan Hongbin; Yang Zhiyong

来源：Neural Regeneration Research, 2008, 3(9): 979-984.

• aspirin
• Bax
• Bcl-2
• cerebral ischemia-reperfusion injury
• cell apoptosis

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.

• 出版日期2008-9
• 单位江南大学