Paeonol improves lipopolysaccharide-induced microcirculatory disturbance in rat mesentery

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Objective: To investigate the effect of paeonol on lipopolysaccheride (LPS)-induced rat mesenteric microcirculatory dysfunctions. Methods: Male Wistar rats were randomly distributed into 5 groups (n=6 in each): Sham group, LPS group, paeonol group, paeonol+LPS group, and LPS+paeonol group. Endotoximia model was conducted by continuous LPS infusion. Changes in mesenteric microcirculatory variables, including diameter of venule, velocity of red blood cells in venule, leukocyte adhesion, free radicals produced in venule and albumin leakage from venule, were observed through an inverted intravital microscope. Meanwhile, the expression of myeloperoxidase (MPO), CD18, intercellular adhesion molecule-1 (ICAM-1), toll-like receptor 4 (TLR4), nuclear factor-kappa B p65 subunit (NF-κB p65), activator protein-1 (AP-1), and Jun N-terminal kinase (JNK) was assessed by Western blot. Results: After infusion of LPS, the number of leukocytes adherent to venular wall, the intensity of dihydrorhodamine 123 (DHR) fluorescence in the venular walls, and albumin leakage from venules were significantly increased, whereas the red blood cell velocity in venule was decreased. All the manifestations were significantly reduced by pre-treatment and post-treatment with paeonol. Moreover, paeonol significantly attenuated the expression of MPO, CD18, ICAM-1, TLR4, NF-κB p65, AP-1 and JNK in rat mesentery after LPS. Conclusions: The results demonstrated that paeonol could protect from and ameliorate the microcirculation disturbance induced by LPS. Abbreviations: AP-1, Activator protein-1; DHR, Dihydrorhodamine-123; FITC, Fluorescein isothiocyanate; H2O2, Hydrogen peroxide; ICAM-1, Intercellular adhesion molecule-1; JNK, Jun N-terminal kinase; LPS, Lipopolysaccheride; MPO, Myeloperoxidase; NF-κB p65, Nuclear factor-kappa B p65 subunit; RBCs, Red blood cells; ROS, Reactive oxygen species; PBST, PBS+Tween 20; PMSF, Phenylmethylsulphonyl fluoride; PVDF, Polyvinylidene-difluoride; TLR4, Toll-like receptor 4; TNF-α, Tumor necrosis factor-alpha.