ISCHEMIA AND ISCHEMIA-REPERFUSION AS A MODIFIER OF GLYCOPROTEIN-P CARRIER PROTEIN FUNCTIONING

Abstract

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Purpose of the work was to estimate the expression of glycoprotein-P (Pgp) in a frontal lobe of brain cortex of Wistar rats in one-side occlusion of common carotid artery, and also the occlusion-reperfusion, and to analyze the correlation dependence between the expression of the carrier and free-radical status of brain tissue. Materials and methods of the study: we have carried out the work using 90 male Wistar rats weighed 250-300 g. Animals were divided into 3 groups; the 1st group included intact animals (n=6); animals which had a modeled ischemia of the brain belonged to the 2nd group; 3rd group included the animals, which had a modeled ischemia of the brain during 30 minutes with further reperfusion. The rats of the first group were exposed to sham operation with opening and sealing of skin covers without carotid ligation. The animals of the second group were divided into the following series: 30 min, 60 min, 1.5 hour, 4 hours, 12 hours, 5 days, and 14 days after the occlusion of common carotid artery, and similar terms for 30 minutes occlusion and further reperfusion for the third group (n=6 in every group for every term of the experiment). Occlusion of common carotid artery was modeled under the ether anesthesia after the opening of soft tissues of animals’ neck. Isolation of right common carotid artery was carried out by means of ligation with further sealing of a wound. After the modeling of occlusion-reperfusion artery was constricted with a vascular clamp during 30 minutes. Histological material was exposed to the standard immunohistochemical processing. We determined a content of TBA-reactive products, level of free sulfhydril (SH) groups, activity of glutathione peroxidase and glutathione-S- transferase. The results obtained were processed with the use of StatSoft Statistica 7.0 program. Results: we have established that Pgp expression dropped on the 12th occlusion by 59.2% (p<0.05) and augmented by 65.9% (p<0.05) on the 5th day of the experiment. In other periods, the rate under study did not differ from the intact animals level (p<0.05). One-side occlusion of common carotid artery with following reperfusion led to the Pgp expression reduction in brain tissue 4 and 12 hours after reperfusion on 61.3% and 74.8% (p<0.05) correspondingly. In other period of the observation the rate under study did not differ relevantly from the values of intact animals (p<0.05). Occlusion of common carotid artery, and occlusion-reperfusion led to the development of the signified oxidation stress in brain tissue. While conducting the correlation analysis we have revealed the dependence between Pgp expression in hematoencephalic barrier and activity of antioxidant enzyme glutathione peroxidase in the brain tissue during the whole investigation (Rs=0.352, p=0.024). Conclusions: One-side deligation of common carotid artery of rats with further reperfusion is accompanied by the expansion of an oxidation stress in the tissue of the frontal lobe of brain cortex, Pgp expression reduction after 12 hours from the moment of occlusion and its augmentation on the 5th day of an experiment One-side occlusion of common carotid artery of rats with further reperfusion is accompanied by the expansion of a signified oxidation stress in brain tissue with Pgp expression reduction in 4 and 12 hours after reperfusion. We have revealed a direct correlation dependence between Pgp expression and activity of glutathione peroxidase in the affected tissue of the frontal lobe of brain cortex.