Effects Of Aspirin Preconditioning On The Expression Of Caspase3 And AIF In Rats Following Focal Cerebral Ischemia And Reperfusion

Objective:To investigate the effects of aspirin preconditioning on apoptosis and expression of Caspase3 and AIF in rats following focal cerebral ischemia and reperfusion and to explore protective effects of aspirin on the neurons and the optimal dosageMethods: The rat middle cerebral artery(MCA) cerebral ischemia/reperfusion(CI/RP) model was established with suture occlusion technique according to classic Zea Longa method and then randomly devided the rats into six groups: normal control group(n=12),sham-opration group(n=12),vehicle group(n=12) and three aspirin preconditioning groups (n=36) with different doses of ASA(low dose: 10mg/kg; middle dose:50mg/kg and high dose:150mg/kg) .ASA was given by gastrogavage for five days and once a day before focal cerebral ischemia. The middle celebral artlery occlusion model was made by the suture method at the sixth day. After conscionsness , the neurologic impairment evalution scores were recorded on Longa 5-point scale. The rats were then beheaded after twenty-four hours. The volume of infarction were measured by TTC staining , the expression of Caspase3 and AIF were detected by immunohistochemistry , and the number of the neuron apoptosis was detected by TUNELResults: 1.The rats of the vehicle group and the ASA precongditioning group both had different neurological impairment after CI/RP. Compared with the vehicle group,the nuerological scores of the aspirin preconditioning groups reduced obviously,the low and middle dose groups both showed significant difference. (P <0.01),the high dose group showed difference (P <0.05).There was no significant difference among aspirin precondtionning groups(P>0.05). 2. Compared with the vehicle group , the volume of infarction significantly reduced in aspirin preconditioning groups ,especially in the low and middle dose groups(P<0.01). There was no significant difference between the low and middle aspirin precondtionning groups(p>0.05);The comparision of the low and high dose group and the comparision of the middle and high group both had difference( P<0.05). 3.Compared with the control group and the sham group , the expression of Caspase3 and AIF and TUNEL positive cells was significantly increased in the vehicle and the aspirin preconditioning groups(P<0.01) . Compared with the vehicle group, the expression of Caspase3 and AIF and TUNEL positive cells was significantly reduced in the aspirin preconditioning group, especially in the low and middle dose groups(P<0.01). There was no significant difference between the low and middle aspirin precondtionning groups(P >0.05);The comparision of the low and high dose group and the comparision of the middle and high group both had difference( P<0.05). Conlusion: 1.Aspirin preconditioning can decrease neurological deficit scores and contributes to the recovery of limbs after CI/RP;2.The effects of aspirin preconditioning can reduce infarction volume after CI/RP; 3. Aspirin preconditioning after CI/RP can inhibit the expression of Caspase3 and AIF and reduce TUNEL positive cells,which might be the mechanism of aspirin neuroprotections;4.The effects of low and middle dose of aspirin preconditioning is superior to the high dose, which suggests that the neuroprotection of aspirin dose not increase with the dose of aspirin adding.