Correlation Analysis of Parameters of Skin Microcirculation and Kinetics of Generation of Reactive Oxygen Species by Blood Cells in Mice with a Genetic Model of Type 2 Diabetes Mellitus

Abstract

In type 2 diabetes mellitus, the regulation of blood flow oscillations in microvessels is disrupted by endogenous factors (products of lipid and carbohydrate metabolism, proinflammatory mediators, reactive oxygen species, etc.). At the same time, blood phagocytes show increased activity in the production of reactive oxygen species, but its association with microvascular disorders has not been established. The aim of the work is to evaluate the relationship between the processes regulating oscillations in blood flow in the microvessels of mouse skin and the kinetics of generation of reactive oxygen species in the blood. The object of the study is a model of type 2 diabetes mellitus in mice with monogenic obesity with the LEPR db/db mutation. The methods included laser Doppler flowmetry to register oscillations in blood flow and chemiluminescence analysis to measure the phagocytosis-dependent intensity of generation of reactive oxygen species. In type 2 diabetes mellitus, the normalized amplitude of oscillations in the myogenic frequency range was higher than in the controls. The kinetics of blood cell responses to opsonized zymosan was also changed: the amplitude, rate of development of the response, and production of reactive oxygen species increased; the lag period and T_max decreased. Based on the Spearman rank correlation, strong correlations were found between the lag period of the response to zymosan and oscillations in cutaneous blood flow in the myogenic and Mayer intervals as well as between the rate of response and oscillations in the endothelial, neurogenic, and Mayer intervals in the controls. In mice with type 2 diabetes mellitus, a strong relationship was found between the response rate and oscillations in the neurogenic interval as well as between T_max and oscillations in blood flow in the endothelial and neurogenic intervals. Thus, the development of type 2 diabetes mellitus affected the relationship of the regulatory components of microcirculation with the reactivity of blood cells, which may be a marker of metabolic disorders.