Effect of notoginsenoside R1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion

To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion (I/R) in mice.

The superior mesenteric artery (SMA) of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-min reperfusion. In another set of experiments, R1 was continuously infused (10 mg/kg per hour) from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell (RBC) velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate transaminase (AST) in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in plasma were evaluated by flow cytometry. E-selectin and intercellular adhesion molecule-1 (ICAM-1) in hepatic tissue were examined by immunofluorescence.

After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1.

R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury. The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.