CORRECTION OF HYPOXIC AND ISCHEMIC GENESIS DISADAPTATION WITH PHOSPHORYLATED DERIVATIVES OF GLYCINE

详细

全文:

Purpose of the work was to analyze individual results of experimental studies on the effectiveness of the phosphorylated derivative of glycine ACF 90-7 under hypoxic damage of various origins and cerebral ischemia. Materials and methods of the study: experiments were carried out using CBA mice, outbred rats, and Wistar rats, cats. Antihypoxic activity was studied on models of acute circulatory, hemic hypoxic tissue (histotoxic) hypoxia, hypercapnia and hypobaric hypoxia. The antiischemic activity of the compounds was studied using the following methods. Clamping both carotid arteries for 10-15 minutes with systemic hypotension to 40 mmHg followed by reduction of cerebral blood flow; occlusion of the left carotid artery for 28 days. We also studied the behavior of animals to study the level of anxiety in the "open field" test, the development of passive avoidance (CRPA) and tested for CRPA safety. To examine the neuroprotective activity of the glycine derivative was administered intraperitoneally at doses of 1, 10, 50 and 100 mg/kg. Statistical analysis was performed in a series of the Student t-test (using pairwise comparisons) between the series on the inversions criterion of the Wilcoxon-Mann-Whitney test. Results: ACF 90-7 glycine derivative increases the resistance of animals to the effects of circulatory, hemic, histotoxic, hypobaric hypoxia. Antihypoxic action of ACF 90-7 is superior to glycine in similar doses. ACF 90-7 exceeds antihypoxic action mexidolon a model of hemic (100 mg/kg) and hypoxic hypoxia (at doses of 10 and 50 mg/kg). Modification of a glycine molecule by introducing there a phosphorylated residues leads to significant changes from the studied parameters. ACF 90-7 in the reperfusion period contribute to adaptation to the damaging effect of ischemia, effectively slowing the depletion of carbohydrate reserves of the body, blocking the fall of post-ischemic recovery of glucose and oxygen by the brain and preventing the development of decompensated metabolic acidosis and progressive accumulation of lactate. We noted that ACF 90-7 is more effective than glycine limits the acid-base equilibrium and the metabolism in the brain. It was also found that the test glycine derivative contributes to the preservation of CRPA and significantly limits the disturbances of orientation and exploratory behavior of animals in the "open field" test in terms of chronic cerebral ischemia. Conclusions: we have established experimentally that ACF 90-7 ability to improve the resistance of laboratory animals to hypoxia and limit the severity of metabolic and behavioral responses of animals in conditions of acute and chronic circulatory cerebral ischemia. The results presented are the substantiation for the production of a glycine derivative of neuroprotective drug on its basis.