Purpose: to assess the level of catecholamines norepinephrine and dopamine in rat retina with experimental retinopathy of prematurity (EROP) at a time corresponding to the peak of neovascularization.Material and methods. The study was performed on 41 infant Wistar rats (82 eyes). The rats were divided into 2 groups: the experimental group (with EROP, n = 21) and the control group (n = 20). In order to reproduce the EROP, the newborn rats were placed for 14 days in the incubator together with their mother. Every 12 hours, the oxygen concentration in the incubator ranged from 60 to 15 %. The control group consisted of pups who were held in conditions with a normal oxygen content (21 %) from the moment of birth. The pups were withdrawn from the experiment on the 10th, 14th, 23rd and 28th day, whereupon they were subjected to binocular enucleation followed by histological examination, in addition, the content of noradrenaline and one of the metabolites of dopamine (L-DOPA) was determined in retinal samples of the eyeballs obtained on the 23rd day by highly effective liquid chromatography technique with electrochemical detection.Results. Histological examination showed that in our EROP model the neovascularization peak occurs on the 23rd day of the experiment. At this time rat pups with EROP showed a significantly lower retinal L-DOPA level as compared to the control values (13.99 ng/g and 30.5 ng/g, respectively), and the norepinephrine level significantly exceeded such values (63.7 ng/g and 7.69 ng/g, respectively).Conclusion. A relative deficiency of dopamine and a relative excess of norepinephrine of the rat pups with EROP is noted at the time of the highest vascular activity of the retina. The obtained data confirm anti-angiogenic properties of dopamine and pro-angiogenic properties of noradrenaline in the second phase of EROP development.
Цель -изучить участие дофамина и норадреналина в патогенезе ретинопатии недоношенных (РН) на оригинальной крысиной модели заболевания. Материал и методы. Экспериментальные животные -41 новорожденный крысенок породы Вистар (82 глаза) -были разделены на 2 группы: опытную -крысята с экспериментальной РН (ЭРН) (n = 21) и контрольную (n = 20). Крысят выводили из эксперимента на 7-е, 14-е, 23-и и 28-е сутки жизни. Всем животным в указанные сроки проводили бинокулярную энуклеацию, из глазного бокала выделяли сетчатку. В супернатанте сетчатки определяли содержание норадреналина, дофамина и предшественника дофамина -L-3,4 дигидроксифенилаланина (L-ДОФА) при помощи обращенно-фазовой высокоэффективной жидкостной хроматографии с электрохимической детекцией (Amperometric detector LC-4B, Bioanalytical Systems, США) при потенциале 850 мВ. Результаты. На 7-е сутки, соотве тствующие существованию аваскулярных зон сетчатки в обеих группах животных, достоверных различий по содержанию моноаминов в сетчатке крысят с ЭРН и в контрольной группе не выявлено. На 14-е сутки содержание норадреналина, дофамина и L-ДОФА в сетчатке опытной группы было достоверно повышено по сравнению с контролем. На 23-и сутки, соответствующие пику неоваскуляризации в применяемой модели ЭРН, уровень норадреналина в сетчатке крысят опытной группы был достоверно выше, а уровень L-ДОФА достоверно ниже, чем в группе контроля; уровень дофамина был сравним в обеих группах и сопоставим с уровнем L-ДОФА в контрольной группе. На 28-е сутки, соответствующие началу регресса ЭРН со снижением сосудистой активности, содержание дофамина и L-ДОФА оставалось сниженным по сравнению с группой контроля. Заключение. В процессе развития патологической неоваскуляризации в сетчатке крысят с ЭРН нарастает уровень норадреналина с пиком, соответствующим сроку выраженного патологического роста ретинальных сосудов в применяемой модели, что свидетельствует о его проангиогенных свойствах и непосредственном участии в патогенезе РН. Уровень дофамина и L-ДОФА при развитии ЭРН к 14-м суткам повышался по сравнению с 7-ми сутками, что может быть связано с созреванием продуцирующих амакриновых клеток, а затем на 23-и сутки, т. е. на сроке, соответствующем максимальному пику ангиогенеза, отмечалось относительное снижение L-ДОФА. Можно предположить, что недостаток данного моноамина, а значит, и недостаточное проявление антиангиогенных свойств вносит вклад в развитие бесконтрольной неоваскуляризации сетчатки.
The multifactorial nature of the retinopathy of prematurity (ROP) pathogenesis, makes the thorough study of the mechanism of pathological retinal neovascularization actual. However recently the attention of scientists has been attracted by the participation of renin-angiotensin system (RAS) in the development of retinal vasoproliferative diseases. Purpose: to study the role of AT-II in the pathogenesis of experimental ROP (EROP) in the original model of the disease. Material and methods. To reproduce EROP Wistar rats (n = 15) were exposed to the oxygen concentration varying from 60 to 15% every 12 hours for 14 days from the first day after birth followed by room air for 7 days. Throughout the experiment, the room maintained a constant temperature (+26 °C) and light regime (12 hours a day, 12 hours a night) modes. Control rats (n = 12) were born and kept under normal oxygen content (21 %). Batches of EROP (n = 5) and control (n = 4) rats were sacrificed on 7, 14 and 21 days. All rats underwent binocular enucleation, after which every eyeball was opened on the limb, the cornea and lens were removed with the remains of a persistent vascular bag and a hyaloid artery. Retinas were isolated, homogenized and stored at -20 °C. Angiotensin-II (AT-II) in homogenates was measured using the IFA kit. Results. On the 7th day of the experiment, the level of AT-II in the retina of the experimental group rats was 0.19 ± 0.02 pg/mg protein that was significantly higher than in controls (0.12 ± 0.01 pg/mg protein). On the 14th and 21st days concentrations of AT-II in EROP and control groups had no significant difference. Conclusion. On the 7th day of the experiment, i.e. at the period corresponding to the existence of avascular retinal zones in both groups concentration of AT-II in the retinas of rats with EROP was significantly higher than in controls. This fact indicate the role of this proangiogenic factor in the induction of pathological neovascularization in ROP. Possible prognostic function of this parameter during the period before ROP manifestation has undoubted practical significance.
Atherosclerotic cardiovascular diseases substantially have contributing to mortality and structure of disability in developed countries. Metabolic syndrome is a cluster of clinico-biochemical changes with the most aterogenic potential.Objective: to determine trends of early stages of metabolic syndrome and its relationship with the initial atherosclerosis in young and middle-aged men. Have been examined 436 men with an assessment symptoms of metabolic syndrome, as well as signs of subclinical atherosclerosis. The young men with initial manifestations of metabolic syndrome were characterized by the classical cardiovascular risk factors. According to the results of the study have been already diagnosed dyslipidemia, violation of apolipoproteides fractions, postprandial hyperglycemia at the initial stage of metabolic syndrome in this category of patients. have been proposed assessment of waist circumference, degree of diastolic blood pressure and postprandial glycemia as the most sensitive diagnostic markers of cardiovascular lesions in primary manifestations of metabolic syndrome.
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