Морфофункціональні та біохімічні особливості системи еритрону за умов цукрового діабету 1-го типу

iNOS на фоне интенсификации свободнорадикальных процессов является одной из причин развития оксидативного стресса и метаболической интоксикации, а также приводит к торможению физиологической регуляторной функции NO и проявлению его цитотоксического действия. Обнаружено, что аминогуанидин как селективный ингибитор iNOS влияет на процесс образования и распадения депо NO, контролируемое скоростью и интенсивностью нитрозилирования гемоглобина, а также на кислородтранспортную функцию крови, тем самым, облегчая диссоциацию оксигемоглобина, что является положительным коррегирующим фактором при гипоксическом состоянии, которое возникает при данной патологии.Предложено на основе аминогуанидина вести поиск и разработку препаратов для предупреждения развития или коррекции диабетических осложнений.

Ключевые слова: сахарный диабет 1-го типа, эритроциты, NO-синтаза, гемоглобин, нитрозилирование, аминогуанидин.

SUMMARY

Lyuta M.Ya. Morphofunctional and biochemical features of erythron system under type 1 diabetes mellitus. - Manuscript.

Thesis for a degree of Doctor of Philosophy (Ph.D) in Biology, speciality 03.00.11 - cytology, cell biology, histology. - Institute of Cell Biology of National Academy of Sciences of Ukraine, Lviv, 2007.

Dissertation is devoted to the investigation of biochemical mechanisms mediated changes in morphologic and functional state of erythroid cells and the approaches to correct metabolic processes responsible for appearing and development of type 1 diabetes mellitus (DM) complications.

Revealed changes in erythron system, such as increase of total quantity and daily production of retyculocytes as well as decrease of percentage of polychromatophilic and oxyphilic normocytes under type 1 DM, illustrate the mechanism of the anemia development at cellular level. Increased fetal hemoglobin is a compensatory reaction of organism on development of tissue hypoxia under DM.

Electronic microscopy of the surficial architectonics of erythrocytes detected augmentation of polymorphism in erythrocyte population and the presence of transformed cells in blood under experimental DM which reflect disorders of membrane structure and erythrocyte metabolism. It was shown that the basis of the biochemical impairments which cause the changes in structural and functional state of erythrocytes under type 1 DM, is the significant increase in nitrogen oxide (NO) production resulting in changes in ratio between NO synthase isozymes due to inhibition of endothelial constitutive form and increase in activity of inducible NO synthase (iNOS). Increased activity of iNOS together with intensification of free radical processes induce development of oxidative stress and metabolic intoxication under type 1 DM and transform NO effects from protective to cytotoxic. It was revealed that aminoguanidine, the iNOS selective inhibitor, can be the factor modulating production and degradation of NO depot, controlling by velocity and intensity of nitrylation and nitrozylation of hemoglobin. Analysis of hemoglobin-dissociation curves under experimental diabetes indicates positive corrective effect of aminoguanidine on oxygen-transport system of erythrocytes and respiratory function of blood in whole. As a result, facilitation of oxyhemoglobin dissociation is occurred what is a positive corrective factor under hypoxia under DM.

Aminoguanidine is proposed to use for a search of new drugs for treatment and prevention of vascular complications under type 1 diabetes mellitus.

Key words: type 1 diabetes mellitus, erythrocytes, NO synthase, hemoglobin, nitrozylation, aminoguanidine.

8-09-2015, 22:26