Effects Of Indomethacin On Focal Cerebral Ischemia Reperfusion Injure In Rats

ObjectiveTo study the effect of indomethacin preconditioning to the content of IL-1β and CRP in brain tissue in rats after focal cerebral ischemia reperfusion.MethodsEighty-four healthy male SD rats were randomly divided into three groups: sham-operation group, model group and indomethacin preconditioning group, there are twenty-eight rats in each group. The middle cerebral artery occlusion(MCAO) model was made by the method of modified Longa EZ. Sham-operative group only performed the neck incision, isolated the common carotid, internal carotid, external carotid artery, not blocked blood flow by tying into the line. Indomethacin preconditioning group was given indomethacin (5mg/kg) for five days and once a day before focal cerebral ischemia.After middle cerebral artery occlusion for2hours and reperfusion6hours,12hours,24hours,48hours, the neurological deficit was evaluated.At the appropriate point in time the head was disassociated and the brain was unloaded, the pathological changes in brain tissue were observed by using HE staining, and the content of IL-1p and CRP of the brain tissue were tested by immunohisto chemical analysis.Results1. After middle cerebral artery was blocked for2h, there were the varying severity of symptoms of neurological deficits; compared with the model group, the neurological deficit score of indomethacin preconditioning group were significantly reduced at each time points after ischemia-reperfusion (P<0.05).2. The HE staining of brain tissue in model group displayed:nerve cells in ischemic core was missing or unclear, normal tissue neurons structure and glial cells disappeared, showing that cell swelling, nuclear shrinkage, and even the formation of morphological changes of necrosis such as nuclear debris, and nuclear dissolution. The HE staining of brain tissue in the sham-operation group displayed: there were no edema, degeneration and necrosis, nuclear morphology was regular, into a round, located in the central of cell body, with a light color, nerve cells arranged in neat, nucleolus was clear. In indomethacin preconditioning group the changes above were between sham-operation group and model group, were lighted compared with model group.3.The expression of IL-1β was detected by immune-histochemical staining analysis:compared with the sham group, the expression of IL-1β in model group and indomethacin preconditioning group increased after ischemia-reperfusion6h in the ischemic brain tissue,24h reached the peak, and48h down, but still higher than the sham-operation group (P<0.05); compared with the model group, the expression of IL-1β in indomethacin preconditioning group significantly decreased in ischemia-reperfusion at each time points (P<0.05); there were only a few positive cells in sham-operation group.4.The expression of CRP was detected by immune-histochemical staining analysis:compared with the sham group, in the ischemic brain tissue, the expression of CRP in model group and indomethacin preconditioning group increased after ischemia-reperfusion6h,24h reached the peak, and48h down, but still higher than the sham-operation group (P<0.05); compared with the model group, the expression of CRP in indomethacin preconditioning group significantly decreased in ischemia-reperfusion at each time points(P<0.05); the sham group showed very few positive cells.ConclusionsIndomethacin has certain cerebroprotective effects against cerebral ischemia reperfusion injury in rats, which mechanism is related to the inhibition of IL-1β and CRP expression in brain tissue.