[Mechanism of Dalbergiae Odoriferae Lignum flavonoids in improving microcirculatory disorders based on neutrophil...

This study investigated the effects of Dalbergiae Odoriferae Lignum flavonoids(DOLF) on microcirculatory disorders through the regulation of neutrophil extracellular traps(NETs). Sixty SPF-grade male Sprague-Dawley(SD) rats were randomly divided into a sham operation group, a model group, a nicorandil group(1 mg·kg~(-1)), and low-, medium-, and high-dose DOLF groups(1, 2, and 4 g·kg~(-1), respectively), and were administered the corresponding treatments by gavage for 7 consecutive days. A model of microcirculatory disorders was established by injecting polyethylene microspheres into the left ventricle. The assessed parameters included blood flow, arterial pressure, and left ventricular pressure; plasma viscosity, whole blood viscosity at low, medium, and high shear rates, fibrinogen levels, and platelet function parameters; pathological changes in the heart, liver, lungs, kidneys, and brain observed by hematoxylin-eosin(HE) staining; serum levels of creatine kinase(CK), creatine kinase-MB(CK-MB), alanine aminotransferase(ALT), aspartate aminotransferase(AST), glucose(GLU), and creatinine(Crea); microvascular morphological changes analyzed using AngioTool software combined with the Poiseuille formula; changes in NETs markers myeloperoxidase(MPO) and citrullinated histone H3(CitH3) in rat heart and brain tissue detected by tissue immunofluorescence; serum levels of tumor necrosis factor-α(TNF-α), reactive oxygen species(ROS), and interleukin-1β(IL-1β) measured by enzyme-linked immunosorbent assay(ELISA); changes in MPO and CitH3 levels in NETs derived from neutrophils isolated from rat peripheral blood detected by cellular immunofluorescence; and protein expression levels of MPO, peptidylarginine deiminase 4(PAD4), TNF-α, and interleukin-6(IL-6) in myocardial tissue determined by Western blot. The results showed that, compared with the model group, DOLF improved hemodynamic abnormalities and microcirculatory dysfunction, and ameliorated hemorheological abnormalities in rats. DOLF also alleviated inflammatory cell infiltration and other pathological changes in the heart, liver, lungs, kidneys, and brain; lowered serum levels of CK, CK-MB, AST, ALT, GLU, and Crea; reversed the decreases in microvascular density, diameter, and area, as well as the increases in porosity and blood flow resistance caused by microcirculatory dysfunction; reduced serum levels of TNF-α, IL-1β, and ROS; inhibited NETs formation; and decreased the protein expression of MPO, PAD4, IL-6, and TNF-α in myocardial tissue. These findings suggest that DOLF may improve microcirculatory dysfunction by regulating pathways related to NETs formation, indicating its potential therapeutic value.