In the Sham group and TSA group, there was no signicant change in the DHR uorescence ratio around the venular wall throughout the observation. 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 A-769662 in the adhesion of leukocytes, production of oxygen radicals in the venular wall, albumin efflux and enhanced mast cell degranulationin 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, pre- or post-treatment with TSA signicantly 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 exhibited 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. Keywords:Salvia miltiorrhiza, Leukocyte adherence, Oxygen-free radicals, Albumin leakage, Ischemia-reperfusion == INTRODUCTION == Ischemia-reperfusion (I/R) injury occurs in a wide range of situations, including trauma, vascular reflow after contraction, percutaneous transluminal coronary angioplasty, thrombolysis treatment, organ transplantation, and hypovolemic shock with resuscitation[1], leading to systemic disorders with high morbidity and mortality. I/R-induced microcirculatory disturbance is the pathological basis of I/R injury, manifesting as a complex process that includes endothelial cell dysfunction, enhanced adhesion of leukocyte, macromolecular efflux, production of reactive oxygen species, and mast cell degranulation[2]. The insults brought on by I/R in microcirculation interplay with each other in various ways that creates a vicious circle that exaggerates the impact, among which, the explosively produced peroxides injure the vessels[2], promote expression of intercellular cell adhesion molecule-1 (ICAM-1)[3] and leukocyte adhesion molecules CD11b/CD18[4], leading to an increase in the adhesion of leukocytes to venules[5]. On the other hand, the leukocytes adhered to the venular wall, in turn, release peroxides and protease[6-9] that injure the endothelium and basement membrane of vessels, causing the leakage of serum[2]. Besides, the degranulated mast cell induced by I/R[2] release pro-inflammatory factors and vasoactive substances to attack the vessels from outside[8-10]. Clearly, an agent that targets the multiple insults simultaneously would be appealing for management of I/R-induced microcirculatory dysfunction. However, the study in this regard remains limited. Total salvianolic acid (TSA) is the major water-soluble ingredient ofSalvia miltiorrhiza(SM), including 3,4-dihydroxy-phenyl lactic acid (DLA), salvianolic acid A (Sal A), salvianolic acid B (Sal B) and other salvianolic acids[2]. SM and SM-containing preparations have been clinically used in the prevention and treatment of various vascular diseases[2]. Previous studies have shown that pre-treatment with Cardiotonic Pills (CP, the major ingredients of which are DLA and Sal B) attenuated the gut I/R-induced leukocyte adhesion in liver sinusoids and plasma tumor necrosis factor- (TNF-) and endotoxin[11], diminished the thrombi induced by photochemical stimulation in rat mesenteric venules[12], and prevented I/R-induced myocardial microcirculatory disturbance and myocardial damage in rats[13]. DLA attenuated the production of oxygen radicals and the expression of leukocyte adhesion molecules CD11b/CD18 in mesenteric microcirculatory disturbance induced by I/R[14]. Sal A has the potential of anti-oxidation[15-19], and may normalize membrane permeability[19]. Sal B could inhibit endotoxin-induced rat mesenteric microcirculation disturbance, inhibit the expression of adhesion molecule CD11b/CD18, production of hydrogen peroxide and unfavorable oxygen anion[20-22]. However, the extraction process of DLA and A-769662 Sal B is usually complex and the extraction conditions are hard to control, leading to a high cost for DLA and Tal1 Sal B production. On the other hand, TSA, as the major water-soluble ingredient of SM, has the advantage that this extraction procedure is usually manipulated with a high result and low priced quickly. Nevertheless, whether TSA can improve microcirculatory disruption induced by I/R isn’t clear. Therefore, in this scholarly study, we looked into the result of TSA on I/R-induced rat mesenteric microcirculatory dysfunctions. == Components AND Strategies A-769662 == == Reagents == TSA was bought from Kun Ming Feng-Shan-Jian Medical Business (Yun-Nan, China). Dihydrorhodamine 123 (DHR) was from Molecular Probes Ltd. (Eugene, OR, USA). Fluorescein isothiocyanate (FITC)-albumin and toluidine.