| Aspirin (acetylsalicylic acid, ASA) as a nonsteroidal anti-inflammatory agent not only has well-established efficacy in anti- thromboxane A2, but there also have several reports about neuroprotective effects. In this study, we design to investigate its mechanism, effective doses, and effective treatment time-window on focal cerebral ischemia-reperfusion injury (CIRI) in rats.Right middle cerebral artery was occluded by inserting a thread through internal carotid artery for 2 h, and then reperfused for 24 h or 72 h. 6 mg·kg-1 and 60 mg·kg-1 doses of aspirin were ig administrated at reperfusion 0 h. The neuroprotective effects and its mechanism were estimated. 60 mg·kg-1 dose of aspirin was ig administrated at reperfusion 0 h, 1 h or 3 h , respectively. The effects on reperfusion 24 h were measured. The protective effects of ASA on remote-organs injury were also studied.RESULTS:The protective effects and its mechanism of ASA on CIRI rats for 24 h (1) With the use of 6 mg. kg-1 and 60 mg·kg-1 doses of ASA, the brain injured area, cerebral edema of occluded side, and mortality were dramatically reduced, the morphology of the occluded area was improved, most of neurons in the injured regions survived ischemia-reperfusion result, lactate dehydrogenase (LDH) and creatine phosphokinase (CK) in plasma were decreased by 60 mg·kg-1 dose of ASA. (2) With the use of 6 mg·kg-1 and 60 mg·kg-1 doses of ASA, the ratio of prostacyclin (PGI2)/ thromboxane (TXA2) in plasma and the ratio of bcl-2/bax in injured brain tissue were increased, the numbers of apoptotic cells were dramatically reduced. In plasma, nitric oxide (NO) content was significantly decreased and endothlin (ET) level was increased by 6 mg·kg-1 dose of aspirin. In brain tissue of occluded side, malondialdehyde (MDA) content was reduced and adenosine 5'-triphosphate (ATP) level was increased by the 60 mg·kg-1 dose of aspirin. No significant effect on superoxide dismutase (SOD), myeloperoxidase (MPO) and calcineurin (CaN) content were discovered.The protective effects and its mechanism of ASA on CIRI rats for 72 hCompare with CIRI 24 h, the brain injured area was reduced and the morphology of the occluded area was improved, no significant difference in cerebral edema of occluded side, mortality and neuron density were discovered on CIRI rats for 72 h. With the use of 6 mg·kg-1 and 60 mg·kg-1 doses of ASA, the brain injured area, cerebral edema of occluded side, and mortality were dramatically reduced, the morphology of the occluded area was improved, most of neurons in the injured regions survived. (2) Compare with CIRI 24 h, in brain tissue the ATP level decreased deeply, the ratio of bcl-2/bax in injured brain tissue increased, the numbers of apoptotic cells reduced, and CaN activity increased on CIRI rats for 72 h. The ATP level was increased by 6 mg·kg-1 and 60 mg·kg-1 doses of aspirin. The numbers of apoptotic cells were reduced, the ratio of bcl-2/bax in injured brain tissue was increased, and CaN activity was inhibited by 60 mg·kg-1 dose of aspirin. 3. The protective effects and its mechanism of ASA with different treatment time-window on CIRI rats for 24 hThe injured area of brain , and mortality in the three groups were dramatically reduced by 60 mg·kg-1 dose of aspirin. No significant difference was discovered among the three groups. The cerebral edema of occluded side in the three groups were dramatically reduced by 60 mg·kg-1 dose of aspirin, but that was more serious in the group of treatment after reperfusion 3 h than that in other two groups. The morphology and neuron density of the occluded area were improved by 60 mg·kg-1 dose of aspirin, but that in the 0 h group was the best in the three groups. The ATP level was improved by 60 mg·kg-1 dose of aspirin in the group of treatment at reperfusion onset, and no similar effect was discovered in other two groups.4. The protective effects of ASA on remote-organs with CIRI rats (1) With the use of 6 mg·kg-1 and 60 mg·kg-1 doses of ASA, morphologic c...
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