Protective effects of 3,4-dihydroxyphenyl lactic acid on lipopolysaccharide-induced cerebral microcirculatory disturbance in mice

Abstract

This study intended to examine the effect of 3,4-dihydroxyphenyl lactic acid (DLA), a major ingredient of Salvia miltiorrhiza, on lipopolysaccahride (LPS) -induced mouse cerebral cortical microcirculatory disturbance. Velocity of red blood cells in, and albumin leakage from venules, and the numbers of leukocytes rolling on, and adherent to the venular wall were determined by an up-right microscope after LPS (5 mg/kg/h) infusion with or without administration of DLA (5 mg/kg/h). Expression of adhesion molecules CD11b/CD18 and L-selectin on neutrophils, plasma concentration of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were evaluated by flow cytometry. Concentration of TNF-α in supernatants of LPS-stimulated mononuclear cells was evaluated in vitro by flow cytometry as well. LPS exposure significantly increased the number of rolling and adherent leukocytes as well as albumin leakage, and decreased the velocity of red blood cells in venules. In addition, LPS stimulation apparently increased the expression of CD11b/CD18 on neutrophils, the concentration of plasma TNF-α, and the production of TNF-α from mononuclear cells. Treatment with DLA significantly ameliorated LPS-induced insults in mice, including cerebral microcirculatory disturbance, the expression of CD11b/CD18 on neutrophils, and the increased concentration of plasma TNF-α and the production of TNF-α from mononuclear cells.