Effect of notoginsenoside R1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion.
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.
Chen
Wei-Xing
WX
Talsy Microcirculation Research Center, Peking University Health Science Center, Beijing 100083, China.
Wang
Fang
F
Liu
Yu-Ying
YY
Zeng
Qing-Jiang
QJ
Sun
Kai
K
Xue
Xin
X
Li
Xiang
X
Yang
Ji-Ying
JY
An
Li-Hua
LH
Hu
Bai-He
BH
Yang
Jin-Hui
JH
Wang
Chuan-She
CS
Li
Zhi-Xin
ZX
Liu
Lian-Yi
LY
Li
Yan
Y
Zheng
Jun
J
Liao
Fu-Long
FL
Han
Dong
D
Fan
Jing-Yu
JY
Han
Jing-Yan
JY
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*
D036145:Ginsenosides; C072936:notoginsenoside R1