Total salvianolic acid improves ischemia-reperfusion-induced microcirculatory disturbance in rat mesentery

AIM:To investigate the effect of total salvianolic acid(TSA) on ischemia-reperfusion(I/R)-induced rat mesenteric microcirculatory dysfunctions.METHODS:Male Wistar rats were randomly distributed into 5 groups(n = 6 each):Sham group and I/R group(infused with saline),TSA group,TSA + I/R group and I/R + TSA group(infused with TSA,5 mg/kg per hour).Mesenteric I/R were conducted by a ligation of the mesenteric artery and vein(10 min) and subsequent release of the occlusion.TSA was continuously infused either starting from 10 min before the ischemia or 10 min after reperfusion.Changes in mesenteric microcirculatory variables,including diameter of venule,velocity of red blood cells in venule,leukocyte adhesion,free radicals released from venule,albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope.Meanwhile,the expression of adhesion molecules CD11b/CD18 on neutrophils was evaluated by flow cytometry.Ultrastructural evidence of mesenteric venules damage was assessed after microcirculation observation.RESULTS:I/R led to multiple responses in mesenteric post-capillary venules,including a significant increase in the adhesion of leukocytes,production of oxygen radicals in the venular wall,albumin efflux and enhanced mast cell degranulation in vivo.All the I/R-induced manifestations were significantly reduced by pre-or post-treatment with TSA,with the exception that the I/R-induced increase in mast cell degranulation was inhibited only by pre-treatment with TSA.Moreover,preor post-treatment with TSA significantly attenuated the expression of CD11b/CD18 on neutrophils,reducing the increase in the number of caveolae in the endothelial cells of mesentery post-capillary venules induced by I/R.CONCLUSION:The results demonstrated that TSA protects from and ameliorates the microcirculation disturbance induced by I/R,which was associated with TSA inhibiting the production of oxygen-free radicals in the venular wall and the expression of CD11b/CD18 on neutrophils.

Paeonol Improves Lipopolysaccharide-induced Microcirculatory Disturbance in Rat Mesentery

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.