The role of neutrophilic granulocytes in the development of acute lung injury in experimental diabetes mellitus

Abstract

Diabetes mellitus takes one of the first places in the structure of endocrine diseases. Among the complications of diabetes are sufficiently described nephro- and retinopathy, neuropathy, damage to the cardiovascular system. However, changes in the respiratory system and, in particular, the state of the endothelium of the pulmonary hemocapillaries and the morphofunctional state of neutrophilic granulocytes remain poorly understood. The aim of this study was to determine the role of neutrophilic granulocytes in the pathogenesis of acute lung injury in experimental diabetes mellitus. The experiments were performed on 88 white male Wistar rats weighing 170-210 g. The animals were divided into three groups: 1 – intact (n=10); 2 – control (n=40); 3 – experimental (n=38) with a model of diabetes mellitus, which was reproduced by intraperitoneal administration of streptozotocin company “Sigma” (USA), diluted in 0.1 M citrate buffer with pH 4.5, at a rate of 60 mg/kg body weight. An equivalent dose of 0.1 M citrate buffer solution with a pH of 4.5 was intraperitoneally administered to the control group of animals. Pulmonary tissue collection for electron microscopic examination was performed under thiopental anesthesia 14, 28, 42, 70 days after streptozotocin administration. Pieces of lung tissue were fixed in 2.5 % glutaraldehyde solution, followed by fixation in 1 % osmium tetroxide solution. After dehydration, the material was poured into epon-araldite. Sections obtained on an ultramicrotome “Tesla BS-490” were studied in an electron microscope “PEM-125K”. It was found that in the early stages of diabetes mellitus (14-28 days) there is a violation of the rheological properties of blood, as evidenced by erythrocyte aggregates, excessive accumulation of neutrophils, their adhesion and aggregation in the hemocapillaries of the alveolar wall. With the extension of the experiment (42-70 days) there is a progressive violation of the ultrastructural organization of hemocapillaries of the alveolar wall and pronounced changes in the rheological properties of blood. Erythrocyte sludges and leuco-platelet aggregates are determined in the lumen of microvessels. Increased permeability of hemocapillaries of the alveolar wall leads to the emigration of neutrophilic granulocytes into the interstitium and the lumen of the alveoli with the development of interstitial and intraalveolar edema. Thus, streptozotocin-induced diabetes is accompanied by the development of acute lung damage in the pathogenesis of which the leading role belongs to neutrophilic granulocytes. The nature and severity of changes in the lungs depends on the duration of exposure to hyperglycemia.