| Objective To study the effects of PPARy agonist pioglitazone preconditioning on cerebral ischemia/reperfusion and investigate the possible mechanism.Method There are two parts in this experiment. Middle cerebral artery occlusion mODel was stablished. The first part:adult male SD rats were randomly divided into the following groups:Control(n=8), I/R+pioglitazone(n=8) (high dose,20mg/kg·d, I/R+pioglitazone(n=8) (low dose,15mg/kg·d), single drug preconditioning(n=3) (20 mg/kg-d),Sham(n=3). The rats were given pioglitazone everyday from 7 days before making model. NeurologICAl score was measured at 24h the onset of reperfusion. Rats were decapitated and measured infarct volume and brain edema by TTC stain at 24h after operation. The second part:the animal groups, making model and the way of giving pioglitazone were the same as the first part. Rats were sacrificed at 24h after reperfusion. The expression and content of PAF and P-selectin were measured through immunohistochemistry and ELISA method.Result Pioglitazone preconditioning significantly reduced the neurogical scores in 12 scores method (p＜0.05, HP, LP vs. Control), infarct volume of HP and LP group reduced 44.71% and 29.46% by Control group (p＜0.05, HP, LP vs. Control), brain edema of HP and LP group reduced 29.90% and 8.23% by Control group (p＜0.05, HP vs. Control) at 24h after the onset of reperfusion. The expression of PAF (p＜0.05, HP vs. Control) and P-selectin (p＜0.05, HP, LP vs. Control) of infarct side cortex reduced in HP and LP group compared to the Control group. In HP and LP group the content of PAF (p＜0.05, HP vs. Control) and P-selectin (p＜0.05, HP vs. Control) of infarct side cortex as well as the content of PAF and P-selectin (p＜0.05, HP vs. Control) of basal ganglia diminished compared to Control group through ELISA method. The PAF (p＜0.05, HP vs. Control) and P-selectin change percentage at basic condition to 24h after reperfusion reduced in HP and LP group compared to Control group.Conclusion PPARy agonist pioglitazone preconditioning reduced the ischemia/reperfusion injury and offers neuroprotection. The neurological score, infarct volume, brain edema were improved. The neuroprotection may be associated with the expression and content of PAF and P-selectin diminishing in the infarct side cortex and basal ganglia. It suggested that the possible mechanism of pioglitazone preconditioning may be against the ischemia/reperfusion injury through regulating the inflammatory response. |
PDF Full Text Request