Rtail R. Morphological Features of Skeletal Muscles Regeneration Under the Condition of Experimental Hyperglycemia

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0821U100755

Applicant for

Specialization

  • 222 - Медицина

23-04-2021

Specialized Academic Board

ДФ 55.051.011

Sumy State University

Essay

The dissertation is devoted to the study of structural features of skeletal muscle regeneration of rats at different stages of restorative histogenesis under the influence of chronic hyperglycemia, as well as to elucidate the possibility of correcting the process of muscle recovery under chronic hyperglycemia by platelet-rich plasma. 140 white laboratory male rats (age – 7-9 months) were used for experiment. All animals were divided into four groups: I – control group – animals with mechanical injury of the triceps surae muscle (TSM) (40 rats); II – animals with simulated chronic hyperglycemia (CH) and TSM mechanical injury (40 rats); III – animals with experimental CH, TSM and platelet-rich plasma (PRP) injection into muscle damage area (40 rats); IV-A (10 rats) and IV-B (10 rats) animals for glucose homeostasis evaluation and experimental CH confirmation. The rats of II, III and IV-B groups have been consuming 10 % aqueous fructose solution instead of drinking water during 2 weeks. Then single intraperitoneal injection of streptozotocin (40 mg/kg, Sigma-Aldrich, USA) and nicotinic acid (1 mg/kg) for each animal was performed. Mechanical injury of TSM was modeled in rats of I, II and III groups 60 days after CH simulation. Muscle trauma was reproduced by linear incision perpendicular to muscle fibers course followed by wound edges comparison and stitching. The morphological features of skeletal muscle regeneration in all groups were studied at 3, 7, 14, and 28 days after mechanical injury using organometric, laboratory, morphometric, microscopic, ultramicroscopic, chemical-analytical and statistical methods. Moreover, structurally altered macrophages, vacuoles, vesicles of various sizes, vessels of the microcirculatory tract with imperfect walls, as well as destructively altered myosatellitocytes and remnants of organelle and myofibr bundles were observed in the posttraumatic regenerate. The histological analysis revealed a large number of microcirculatory vessels of various calibers and diameters. Ultrastructural analysis showed that the cytoplasm of the newly formed muscle cells contained mostly regular-shaped nuclei, a significant amount of mitochondria in the perinuclear space, and the bundles of myofibrils with a wavy and partially ruptured Z-line. Scientific novelty. It was established that chronic hyperglycemia reduces the intensity of new muscle fibers formation during the restorative myohistogenesis as well as leads to disruption of intracellular organization of myosimplasts, significantly inhibits the process of angiogenesis, accelerates the formation of connective tissue elements, weakens the migration of agranulocytes into the defect site, and contributes to the persistent of granulocytes. It was found that chronic hyperglycemia affects the macro- and micronutrient composition of skeletal muscle during their post-traumatic regeneration, leading to a decrease in calcium, iron, zinc and copper, and the accumulation of sodium and magnesium. For the first time, the morphological study of the effect of platelet-rich plasma on the course of post-traumatic skeletal muscle regeneration under the influence of chronic hyperglycemia was conducted. It has been proved that autologous platelet-rich plasma injection significantly promotes the skeletal muscle recovery process in rats with chronic hyperglycemia, shifting it away from fibrosis toward the complete muscular organ formation. Practical meaning. The disclosure of structural features of skeletal muscle recovery in rats under the condition of chronic hyperglycemia significantly expands the knowledge about the specifics of reparative regeneration of striated muscles under the influence of damaging factors, as well as paves the way for more effective and in-depth search for potential ways of skeletal muscle recovery corrections in patients with metabolic disorders. The use of platelet-rich plasma to improve skeletal muscle regeneration under chronic hyperglycemia has been experimentally proven, which suggests the use of this method to enhance the regeneration of striated muscle in people with chronic hyperglycemia.

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