Effects Of Aspirin Pharmacological Preconditioning On Apoptosis And Expression Of Bcl-2 And Bax In Rats Following Focal Cerebral Ischemia And Reperfusion

Objective:To investigate the effects of aspirin preconditioning on apoptosis and expression of Bcl-2 and Bax in rats following focal cerebral ischemia and reperfusion.To explore protective effects of aspirin on the neurons and the optimal dosage.Methods:Established the rat MCA cerebral ischemia/reperfusion(CI/RP)model with suture occlusion technique according to modified Zea Longa method and then the rats were randomly devided into four groups:one contrast groupand three therapy groups with different dose of ASA(low dose:10mg/kg,middle dose,50mg/kg and large dose,150mg/kg)via a lavage rote right before focal cerebral ischemia.After consciousness the neurologic impairment evaluation score were recorded.The rats were then killed at the sixth day and some of the brains were removed to measure the infarct volume,the others were detected apoptosis by TUNEL technology and protein bcl-2,protein bax levels by immunohistochemistry technology.Results:Neurologic impairment in various degree appeared in the contrast group rat after CI/RP.The infarct brain area,where showed white colour because not stained by TTC,can be distinguished clearly to the normal brain where showed red colour.TUNEL positive cell which can represent apoptosic neurons mainly appeared in the penumbra.Propein Bcl-2 and Bax can be determinated by immuno-histochemistry technology.Bcl-2 positive cells which concentrated highly in the penumbra appeared an relative normal shape with an completed nuclei,on the contrary,Bax positive cells which concentrated near to the necrosis core appeared an fusiform shape with an shrinkaged nuclei.When different doses of ASA were lavaged to the rats in the theree therapy groups,the results of every detection items described above changed as follows:the neurologic impairment lessened,the infarct volume reduced,the number of TUNEL positive cells decreased, the protein Bcl-2 expression increased as well as protein Bax expression reduced.Conclusion:1.The effect of ASA pharmacological preconditioning can reduce infarct volume;2. The effect of ASA pharmacological preconditioning can decrease neurologic impairment;3.The effect of ASA pharmacological preconditioning can inhibit the neuron apoptosis of ischemic area via enhanced protein Bcl-2 expression as well as reduced protein Bax expression.4.The effect of low and middle dose of ASA show an superiority to the large dose,which means that the neuroprotection of ASA does not present an increasing level as the dose of ASA adds.