Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery.
OBJECTIVE
To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system.


METHODS
LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation, such as diameters of arterioles and venules, velocity of RBCs in venules, leukocyte rolling, adhesion and emigration, free radicals released from post-capillary venules, FITC-albumin leakage and mast cell degranulation, were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile, the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils, and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro.


RESULTS
The continuous infusion with LPS resulted in a number of responses in microcirculation, including a significant increase in the positive region of venule stained with Monastral blue B, rolling and adhesion of leukocytes, production of oxygen radical in venular wall, albumin efflux and enhanced mast cell degranulation in vivo, all of which, except for the leukocyte rolling, were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils, and the expression of ICAM-1 in HUVECs were increased by exposure to LPS, and they were attenuated by compound Danshen injection.


CONCLUSIONS
These results suggest that compound Danshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance.
Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, Beijing 100083, China. kan@chuigaku.co.jp
Jing-Yan
JY
Han
Yoshinori
Y
Horie
Soichiro
S
Miura
Yasutada
Y
Akiba
Jun
J
Guo
Dan
D
Li
Jing-Yu
JY
Fan
Yu-Ying
YY
Liu
Bai-He
BH
Hu
Li-Hua
LH
An
Xin
X
Chang
Man
M
Xu
De-An
DA
Guo
Kai
K
Sun
Ji-Ying
JY
Yang
Shu-Ping
SP
Fang
Ming-Ji
MJ
Xian
Masahiro
M
Kizaki
Hiroshi
H
Nagata
Toshifumi
T
Hibi
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000494:pharmacology*; D042783:Endothelial Cells / Q000378:metabolism; D004731:Endotoxins; D006801:Humans; D066298:In Vitro Techniques; D007261:Infusions, Intra-Arterial; D036904:Leukocyte Rolling / Q000187:drug effects; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D008297:Male; D008407:Mast Cells; D008638:Mesenteric Arteries / Q000503:physiopathology*; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D009504:Neutrophils / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D027561:Salvia miltiorrhiza; D014471:Umbilical Veins / Q000166:cytology
D015815:Cell Adhesion Molecules; D004365:Drugs, Chinese Herbal; D004731:Endotoxins; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; C028972:dan-shen root extract