Recombinant thrombomodulin improves the visceral microcirculation by attenuating the leukocyte-endothelial interaction in a rat LPS model

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• 作者：Toshiaki Iba ; ^{toshiiba@cf6.so-net.ne.jp} ; Koichiro Aihara ; Shin Watanabe ; Youichi Yanagawa ; Masaaki Takemoto ; Atsushi Yamada ; Daphne Yang
• 关键词：anticoagulant therapy ; severe sepsis ; microcirculation ; activated leukocyte ; high-mobility group box 1 ; intravital microscope
• 刊名：Thrombosis Research
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：131
• 期：4
• 页码：295-299
• 全文大小：502 K

文摘

Introduction

Abnormalities in vascular endothelial function play an important role in the development of septic organ dysfunction. The aim of this study was to examine the effect of recombinant thrombomodulin (rTM) on leukocyte-endothelial interaction and subsequent malcirculation in endotoxemia.

Materials and Methods

Wistar rats were administered with either low, medium or high dose of rTM (n = 7 each) 2 hours after lipopolysaccharide (LPS) infusion. Mesenteric microcirculation after the treatment was observed under the intravital microscopy. In another series (n = 5 each), plasma levels of high-mobility group box 1 (HMGB1) levels were measured at 5 hours after LPS infusion.

Results

Microscopic findings revealed suppression in leukocyte adhesion, thrombus formation and endothelial damage with the treatment by rTM. However, high-dose rTM tended to increase the bleeding events. Thus, blood flow was better maintained with medium-dose rTM (P < 0.05). The increase in HMGB1 level was significantly suppressed by medium and high-dose rTM (P < 0.05, respectively).

Conclusions

rTM demonstrated a protective effect on microcirculation through the inhibition of leukocyte-endothelial interaction and suppression of HMGB1.