Oxidative stress and neutrophil activation leading to an increase in myeloperoxidase (MPO), elastase and neutrophil extracellular trap (NET) levels in blood are considered as pathogenic mechanisms responsible for the development of extremity damage in people with type 2 diabetes mellitus (T2DM). The aim of this study was to analyze the relationship between factors, associated with neutrophil activation, and the length of the initial phase of wound healing (the inflammatory phase) in T2DM patients. Patients were divided retrospectively into three groups depending on the damage extent: group 1 (wound on toe) < group 2 (wound on foot) < group 3 (wound on lower leg). Compared to the control group (healthy volunteers), T2DM patients at admission to hospital had significantly (p<0.05) increased levels of blood glucose and glycated hemoglobin (groups 1-3), ESR (groups 1 and 3), blood neutrophil count (groups 2 and 3), plasma MPO concentration (groups 1-3) and blood NET concentration (group 3) and decreased levels of plasma thiols (groups 1-3) and erythrocyte glutathione peroxidase activity (groups 2 and 3). The length of hospital stay after surgical procedures corresponded to the length of the inflammatory phase of the wound healing process and correlated with the number of blood neutrophils in patients before surgery (r=0.72, p<0.05). Leukocytic intoxication index depended on wound area (r=0.59, p<0.05), and it was significantly higher for groups 2 and 3 compared to the control group and group 1. The neutrophil count before surgery in T2DM patients with damage in the lower extremities correlated with the length of the inflammatory phase of wound healing. The correlation found can be attributed to an increase in extracellular MPO and NETs, which, in its turn, results from the activation and degranulation of neutrophils and netosis. Thus, the duration of the inflammatory phase of wound healing depends on specific aspects of systemic inflammation increasing oxidative/halogenative stress and intoxication.
Okislitel'nyĭ stress i aktivatsiiu neĭtrofilov, vedushchuiu k povysheniiu soderzhaniia v krovi mieloperoksidazy (MPO), élastazy i neĭtrofil'nykh vnekletochnykh lovushek (NVL), otnosiat k patogeneticheskim mekhanizmam povrezhdeniia konechnosteĭ pri sakharnom diabete 2-go tipa (SD2). Tsel'iu issledovaniia byl analiz sviazi mezhdu faktorami, kharakterizuiushchimi aktivatsiiu neĭtrofilov, i dlitel'nost'iu nachal'noĭ fazy zazhivleniia rany (fazy vospaleniia) u bol'nykh SD2. Retrospektivno patsienty byli razdeleny na tri gruppy v zavisimosti ot tiazhesti porazheniia nizhnikh konechnosteĭ: gruppa 1 (rana na pal'tse) < gruppa 2 (rana na stope) < gruppa 3 (rana na goleni). Po sravneniiu s kontrol'noĭ gruppoĭ (zdorovye dobrovol'tsy) u patsientov pri postuplenii na lechenie byli dostoverno (r<0,05) povysheny uroven' gliukozy i glikirovannogo gemoglobina (gruppy 1-3), SOÉ (gruppy 1 i 3), soderzhanie neĭtrofilov v krovi (gruppy 2 i 3), kontsentratsiia MPO v plazme krovi (gruppy 1-3) i kontsentratsiia NVL v krovi (gruppa 3), a takzhe snizheno soderzhanie tiolov plazmy (gruppy 1-3) i aktivnost' glutationperoksidazy éritrotsitov (gruppy 2 i 3). Prodolzhitel'nost' prebyvaniia v statsionare posle operatsii sootvetstvovala dlitel'nosti fazy vospaleniia ranevogo protsessa i korrelirovala s soderzhaniem neĭtrofilov v krovi patsientov do nachala lecheniia (r=0,72, r<0,05). Leĭkotsitarnyĭ indeks intoksikatsii zavisel ot ploshchadi rany (r=0,59, r<0,05) i v gruppakh 2 i 3 byl dostoverno vyshe, chem v kontrole i v gruppe 1. Vyiavlennaia korreliatsiia obuslovlena rostom soderzhaniia vnekletochnoĭ MPO i NVL v rezul'tate aktivatsii i degranuliatsii neĭtrofilov i netoza. Takim obrazom, dlitel'nost' fazy vospaleniia pri zazhivlenii rany sviazana s osobennostiami sistemnogo vospaleniia, vedushchego k usileniiu okislitel'nogo/galogeniruiushchego stressa i éndogennoĭ intoksikatsii.
Keywords: blood neutrophils; diabetes mellitus; diabetic foot; myeloperoxidase; neutrophil extracellular traps; oxidative/halogenative stress.