title: Effect of notoginsenoside R1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion.
abstract: OBJECTIVE
  To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion (I/R) in mice.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Talsy Microcirculation Research Center, Peking University Health Science Center, Beijing 100083, China.
authors.forename: Wei-Xing
authors.initials: WX
authors.lastname: Chen
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Liu
authors.forename: Qing-Jiang
authors.initials: QJ
authors.lastname: Zeng
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Xin
authors.initials: X
authors.lastname: Xue
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Ji-Ying
authors.initials: JY
authors.lastname: Yang
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: An
authors.forename: Bai-He
authors.initials: BH
authors.lastname: Hu
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Yang
authors.forename: Chuan-She
authors.initials: CS
authors.lastname: Wang
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Li
authors.forename: Lian-Yi
authors.initials: LY
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Zheng
authors.forename: Fu-Long
authors.initials: FL
authors.lastname: Liao
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Fan
authors.forename: Jing-Yan
authors.initials: JY
authors.lastname: Han
mesh_terms: D000818:Animals; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology*; D007422:Intestines / Q000098:blood supply; D008102:Liver Circulation / Q000187:drug effects*; D008107:Liver Diseases / Q000517:prevention & control*; D017538:Mesenteric Artery, Superior; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects; D005894:Panax; D015427:Reperfusion Injury / Q000188:drug therapy*
chemical_list: D036145:Ginsenosides; C072936:notoginsenoside R1