Hresko N. Morphological peculiariaties of the rat’s colon under normal conditions and under the influence of opioid

This dissertation presents a study of the rat's colon morphology under normal conditions and at various stages of the experimental impact of an opioid (nalbuphine). The following methods of the studies have been used in the scientific work: injection, histological and electron microscopic, morphometric and statistical methods. The obtained results of the study provide a deeper insight into pathomorphology of the colon lesion under the influence of opioids, create the basis for further studies of pathogenesis of the opioids effect on the systems and organs aiming at elaboration of correctional methods and prevention of complications in the clinical application of this group of preparations in cases of both short- and long-term use. Besides, they allow us to assess the risks of occurrence of the colon lesion in the event of the use of opioids by drug addicts with the aim of prevention of complications and selection of a substitution therapy. The results of the work are of practical importance for the morphologists, gastroenterologists and surgeons, as they may serve as a morphological basis for developing the new methods of diagnostics, prevention and treatment of the colon pathology in patients who have to use opiates and opioids during prolonged periods of time and in the drug addicts. The obtained results of the study of structural peculiarities of the white rat's colon wall under normal conditions and under the experimental effect of the opioid appear to be the fundamental data that the researchers can make reference to when attacking the problems of experimental and clinical medicine. There has been observed a clear connection between the depth of restructuring of the white rat's colon hemomicrocirculatory bloodstream components and the reliably changed values of morphometric indices in case of nalbuphine injections during 6 weeks. Disorders in the colon angioarchitecture in the result of the prolonged injection of nalbuphine were manifested through deformation of arterioles and unevenness of their lumen, destruction of the capillary net, considerable dilatation and deformation of venules. There has also been observed a development of additional arteiolovenular anastomoses and appearance of microaneurysms. The rats that had injections of nalbuphine during six weeks microscopically showed dystrophic and necrobiotic changes in adluminal colonocytes and caliciform cells, decreased secretion of mucus and changes in its composition as well as the increased proliferation of colonocytes in the bottom of Lieberkuhn's crypts, dilatation and engorgement of microcirculatory bloodstream, sub-mucous membrane, muscular tunic and serous layer. Leucocytic infiltration of ground substance of mucous membrane connective tissue, sub-mucous tissue as well as muscular and serous tunics of the colon that has been morphometrically manifested by the changes in the thickness of all its tunics. The main link in the development of the colon wall vascular pathology under the effect of nalbuphine on the ultrastructural level is the mitochondrial insufficiency of endotheliocytes and myocytes that is structurally manifested by the lysis of external membranes and cristaes of these organelles, which leads to the deficiency of energy supply of intracellular synthetic reactions and reparative processes. Development of ultrastructural transformations of the submicroscopic organization of the colonocytes' epithelial plate, cells of the proper mucous plate loose connective tissue and smooth myocytes of the muscle plate of the mucous membrane of the colon under the effect of nalbuphine shows the increasing degree of expression of dystrophic changes that by the end of the experiment pass into destructive phase. During the first two weeks the state of ultrastructure shows an increase in compensatory-adaptive reactions in colonocytes of the epithelial plate, in the cells of the loose connective tissue of the proper mucous plate and smooth myocytes of the muscle plate in response to the effect of nalbuphine. Further on, dystrophic changes develop into destructive, that are manifested through the focal lysis of the nuclear membrane, outer membranes and crystae of mitochondria, and canaliculi of the endoplasmic reticulum in the listed cells. On the sixth week of exposure to nalbuphine irreversible dystrophic and destructive derangement develops of the ultrastructure of colonocytes’ epithelial plate, cells of the proper mucous plate loose connective tissue and smooth myocytes of the muscle plate.