Морфофункціональні зміни в легенях за умов алоксанової гіперглікемії (анатомо-експериментальне дослідження)

Abstract

Дисертаційна робота присвячена вивченню впливу алоксанової гіперглікемії на закономірності структурної перебудови і зміни біоелементного складу легень у тварин різних вікових груп та встановленню можливості їх корекції препаратом кверцетином. Серед тварин різних вікових категорій найбільший ступінь морфологічних змін у легенях, які мали емфізематозне спрямування, виявили в молодих щурів, оскільки їм був притаманний рестриктивний компонент порушення дихальної функції, що підтверджувалося морфометрично – зростанням показників співвідношення А і Б в 1,6 (р < 0,0001) та 1,8 (р < 0,0001) раза (відносне збільшення ширини входу в альвеолу та ширини провідної бронхіоли до глибини альвеоли, яка зменшувалася) зі зростанням терміну алоксанової гіперглікемії. Виявили, що застосування кверцетину ефективне для підтримання функцій легеневих структур за умов хронічної гіперглікемії.

Диссертационная работа посвящена изучению влияния аллоксановой гипергликемии на закономерности структурной перестройки и изменения биоэлементного состава легких у животных разных возрастных групп и установлению возможности их коррекции препаратом кверцетином. Среди животных разных возрастов наибольшую степень морфологических изменений в легких, которые имели эмфизематозное направление, обнаружили у молодых крыс, поскольку им был характерен рестриктивный компонент нарушения дыхательной функции, что подтверждалось морфометрически – возрастанием показателей соотношения А и Б в 1,6 (р < 0,0001) и 1,8 (р < 0,0001) раза (относительное увеличение ширины входа в альвеолы и ширины респираторной бронхиолы к глубине альвеолы, которая уменьшалась) с увеличением срока аллоксановой гипергликемии. Обнаружили, что применение кверцетина эффективно для поддержания функций легочных структур в условиях хронической гипергликемии.

The thesis is devoted to the study of the influence of alloxan hyperglycemia on the patterns of structural adjustment and changes in the bioelement composition of lungs in animals of different age groups, as well as the possibility of their correction with the drug Quercetin. The chemical compound alloxan monohydrate was used to simulate hyperglycemia. The following research methods were used: lung organometry; morphometry of alveolar structures, components of the aerohematic barrier, pulmonary vessels of muscular type, lymphoid follicles; histological examination of lung tissue; quantitative assessment of lung chemical composition; ultramicroscopic examination of the lungs; instrumental examination of the chest; statistical processing of digital data. From the 30th to the 180th day of experiment, pulmonary lymphoid follicles hyperplasia was detected. Muscle hypertrophy of myocytes and mature collagen fibers were observed in pulmonary vessels of muscle type. From the 30th to the 180th day of the experiment, the thickness of the interalveolar septum increased 2,4-fold (p < 0,05); the width of entry into the alveoli increased from the 120th day by 25 % (p < 0,05); up to the 120th day alveoli width increased by 24 % (p < 0,05) but decreased by 8 % up the 150th day (p < 0,05); the width of the leading bronchiole increased from the 30th to the 180th day 1,5 times (p < 0,05). The thickness of the vascular wall increased 3,5 times (p < 0,05) due to the growth of all components. The perimeter of lymphoid follicles increased from the 30th to the 180th day 8 times (p < 0,05). The thickness of the hemato-alveolar barrier increased sharply from the 90th day by 8 % (p < 0,05). The content of bioelements changed as follows: sodium and potassium decreased by 2 % (p < 0,05) and 1,5 % (p < 0,05) by the end of the experiment, respectively, copper, zinc, manganese, iron, magnesium increased by 4 % (p < 0,05), 6 % (p < 0,05), 65 % (p < 0,05), 0,1 % (p < 0,05) and 1 % (p < 0,05) ), respectively. There was a 2-fold increase in Zn/Co ratio (p < 0,05) compared to intact rats. Thickening of the interveal sections due to hypervascularization was observed in mature rats on the 30th day of the experiment, and collagen fibers hypertrophy in their composition was observed on the 60th - on the background of emphysematous transformation of the lungs, which was took place until the end of the experiment. Morphometry revealed that the thickness of the interalveolar septum increased 1,7-fold (p < 0,05) from the 30th to the 180th day; the width of the alveoli increased sharply from the 90th day 1,4 times (p < 0,05), but by the 120th day it decreased slightly by 2 % (p < 0,05) and up to the 180th day was 69,8 ± 0,1 mcm; the width of the leading bronchiole increased from the 30th to the 180th day by 21 % (p < 0,05). The thickness of the hematoalveolar barrier increased sharply from the 90th day by 25 % (p < 0,05), with changes in the thickness of the interstitial space and the thickness of the endothelial cells. There was a 2-fold increase in Zn/Co ratio (p < 0,05) compared to intact rats. In old rats, under light optical examination, collagen fiber hypertrophy was found in the interalveolar septum, and lung air enlargement from the 60th day of the experiment, which showed the phenomena of emphysematous orientation, which increased up to the 180th day of the experiment. The lymphoid follicles were hypertrophied. Pulmonary artery sclerosis was observed from the 30th day of the experiment. The morphometric indices varied as follows: the thickness of the interalveolar septum increased 1,4-fold (p < 0,05) from the 30th to the 180th day of the experiment; the width of the entrance to the alveoli from the 30th to the 180th day increased 1,5 times (p < 0,05); alveoli depth increased sharply from the 120th day 1,3 times (p < 0,05) to the 180th day was 74,4 ± 0,13 mcm; alveoli width increased from the 30th to the 180th day in 1,4 times (p < 0,05); the width of the leading bronchiole increased from the 30th to the 180th day by 1,2 % (p < 0,05). The Zn/Co ratio increased 1,5-fold (p < 0,05) compared to intact animals. Computed tomography of the chest in rats of all ages from the 30th to the 180th day of experiment showed an increase in mediastinal lymph nodes. During two-factor dispersion, the duration influence of hyperglycemia was found to be 47,9 % for the width of the entrance to the alveoli, 42,8 % on the width of the leading bronchiole, 67,7 % on the thickness of the interveolar septum; influence of age factor on 44,4 % for alveoli width, on 42,7 % for alveoli depth. The duration of the experiment significantly influenced 85,5 % of the size of lymphoid follicles. The age of the hemato-alveolar barrier and the thickness of the interstitium influenced the age factor on 50,8 % and 52,2 %, respectively. Sodium concentration was influenced by the duration of hyperglycemia on 59,2 %, potassium - the duration of the experiment and the age factor had the same effect; the concentration of other bioelements was influenced by the age factor. Due to the nature of changes in the structures of the pulmonary tissue, and with the aim of correcting the pathogenetic links of the development of alloxan hyperglycemia, the drug Quercetin was selected in the form of granules. In animals on the background of the drug, compared with rats that did not consume Quercetin, stasis in the pulmonary arteries developed later; its immunomodulatory effect contributed to less active hyperplasia of lymphoid follicles, macrophages. These findings provide grounds for the use of Quercetin for the prevention of early and the treatment of initial complications of hyperglycemia.