Fedorchenko Y. Pathogenetic mechanisms of changes development in respiratory part of lungs in case of experimental diabetes mellitus

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0824U001189

Applicant for

Specialization

  • 222 - Медицина

31-08-2023

Specialized Academic Board

1914

Ivano-Frankivsk national medical university

Essay

Experiments were performed on 88 white male Wistar rats weighing 170-210 grams. The animals were divided into three groups: 1 – intact (n=10); 2 – control (n=40); 3 – experimental (n=38) with a model of DM, which was induced by intraperitoneal injection of streptozotocin from the company «Sigma» (USA), diluted in 0,1 M citrate buffer with pH 4,5, at the rate of 60 mg/kg of body weight. The control group of animals was intraperitoneally injected with an equivalent dose of 0,1 M citrate buffer solution with a pH of 4,5. All manipulations were performed under sodium thiopental anaesthesia at the rate of 60 mg/kg of body weight. The material was collected 14, 28, 42 and 70 days after streptozotocin injection. Conducted biochemical studies and enzyme-linked immunosorbent assays showed that 14 days after the simulation of DM there was an increase in the level of glucose by 222.5%, an intensification of lipoperoxidation processes (an increase in the content of DC by 31.8%, TBA-AP by 36.2%), an increase in the concentration of catalase by 46.6%, MMM254 by 32.9%, MMM280 by 12.7%, an increase in the concentration of OMP356nm by 27.1%, OMP370nm by 18.6%, OMP430nm by 66.9%, OMP530nm by 73.6% in the blood serum compared to control groups of animals. In 28 days after the start of experiment, there was an increase in the content of glucose by 224.4%, DC by 104.4%, TBA-AP by 55.5%, an increase in the level of catalase by 74.8%, MMM254 by 51.7%, MMM280 by 34.0%, an increase in the concentration of OMP356nm by 57.1%, OMP370nm by 48.0%, OMP430nm by 92.4%, OMP530nm by 124.5% in the blood serum compared to the indicators of control groups of animals. In 42 days in the conditions of simulated DM, in the blood serum an increase in the concentration of glucose by 267.6%, an increase in lipoperoxidation (an increase in the level of DC by 112.5%, TBA-AP by 68.4%), an increase in the content of catalase by 29.3%, MMM254 by 69.3%, MMM280 by 64.8%, an increase in the level of OMP356nm by 119.0%, OMP370nm by 117.3%, OMP430nm by 127.9%, OMP530nm by 161.1% was detected in blood serum compared to the indicators of control groups of animals. In 70 days after the simulation of DM in the blood serum an increase in the concentration of glucose by 300.2%, DC by 125.4%, TBA-AP by 88.0%, a decrease in the level of catalase by 28.1%, an increase in the content of MMM254 by 100.4%, MMM280 by 94.5%, an increase in the level of OMP356nm by 132.0%, OMP370nm by 124.4%, OMP430nm by 168.7%, OMP530nm by 207.7% was noted compared to the indicators of control groups. The conducted ultrastructural analysis of the respiratory part of the lungs showed that 14 days after the start of the experiment, a significant number of alveolar macrophages (AM) were in a state of increased functional activity. In alveolocytes of type I (A-I) and alveolocytes of type II (A-II) mitochondria were with a matrix of medium electron-optical density. Cisterns and tubules of the Golgi apparatus (GA) and rough endoplasmic reticulum (RER) were without special structural changes. Lamellar bodies (LB) were of various degrees of maturity, size, and shape. Distinct mitochondria with lighted matrix were found in the cytoplasm of endotheliocytes of hemocapillaries. In 28 days of research swollen mitochondria with single cristae were found in the cytoplasm of A-I. The GA was represented by expanded cisterns. RER tubules were slightly expanded. In 42 days from the beginning of the DM simulation, nuclei of A-I and A-II were with nucleoplasm of low electron-optical density and marginal localization of chromatin. In 70 days of research, hyperhydration phenomena of A-I and A-II continued to persist. For the first time, the patterns of functional and morphological changes in the components of the respiratory part of the lungs in experimental DM have been established based on a comprehensive approach using modern biochemical, enzyme-linked immunosorbent assay, electron-microscopic, and statistical research methods. It has been proven that in the dynamics of DM development, lung injury is accompanied by the intensification of the processes of lipid and protein peroxidation, endogenous intoxication, and activation of pro-inflammatory cytokines. It has been shown that in conditions of simulated DM, the pro- and antioxidant balance shifts towards the predominance of prooxidant mechanisms. For the first time, it has been established that an increase in the concentration of SP-A1 and SP-B in the blood in diabetes can serve as a molecular biomarker of damage to the aerogematic barrier of the lungs, as evidenced by the data of an electron microscopic study. Key words: streptozotocin-induced diabetes, lungs, respiratory part, ultrastructural study, middle mass molecules, lipid peroxidation, oxidative modification of proteins, diene conjugates, TBA-active products, catalase, surfactant proteins, pro-inflammatory cytokines. Branch-Medicine.

Research papers

Zaiats LM, Fedorchenko YuV. The role of neutrophilic granulocytes in the development of acute lung injury in experimental diabetes mellitus. Reports of Morphology. 2022;28(1):5-10 DOI: https://doi.org/10.31393/morphology-journal-2022-28(1)-01

Заяць ЛМ, Федорченко ЮВ. Стан прооксидантної та антиоксидантної систем крові у білих щурів при експериментальному цукровому діабеті. Art of medicine. 2022;1(21):39-43 DOI: 10.21802/artm.2022.1.21.39

Zaiats LM, Fedorchenko YuV. Features of lipoperoxidation and morphological changes of the lungs in experimental diabetes mellitus. World of Medicine and Biology. 2022;3(81):214-18. DOI: 10.26724/2079-8334-2022-3-81-214-218

Заяць ЛМ, Федорченко ЮВ. Особливості цитокінового профілю крові щурів при стрептозотоцин-індукованому діабеті. Art of medicine. 2022;4(24):53-7. DOI: 10.21802/artm.2022.4.24.53

Заяць ЛМ, Федорченко ЮВ. Вміст молекул середньої маси у крові щурів за умов розвитку стрептозотоцин-індукованого діабету. Актуальні проблеми транспортної медицини. 2022;4(70):93-100. DOI: https://dx.doi.org/10.5281/zenodo.7495368

Заяць ЛМ, Федорченко ЮВ. Сурфактантний протеїн А1 (SP-A1) – молекулярний біомаркер ушкодження легень при експериментальному цукровому діабеті. Здобутки клінічної і експериментальної медицини. 2022;4(52):105–9. DOI: https://doi.org/10.11603/1811-2471.2022.v.i4.13505

Заяць ЛМ, Федорченко ЮВ. Патогенетична роль сурфактантного протеїну B у формуванні легеневої патології у тварин при стрептозотоцин-індукованому діабеті. Медична та клінічна хімія. 2022;(4):27–31. DOI: 10.11603/mcch.2410-681X.2022.i4.13568

Заяць ЛМ, Федорченко ЮВ. Окисна модифікація білків у сироватці крові щурів за умов експериментального цукрового діабету. Актуальні проблеми транспортної медицини. 2023;1-2(71-72):190-196. DOI: http://dx.doi.org/10.5281/zenodo.7617874

Files

Similar theses