重组人可溶性血栓调节蛋白对肝窦阻塞综合征模型小鼠的预防作用。

Prophylactic Effect of Recombinant Human Soluble Thrombomodulin for Hepatic Sinusoidal Obstruction Syndrome Model Mice.

机构信息

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan.

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Japan

出版信息

In Vivo. 2020 May-Jun;34(3):1037-1045. doi: 10.21873/invivo.11873.

DOI:10.21873/invivo.11873

PMID:32354890

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7279798/

Abstract

AIM

The present study aimed to examine the effects of prophylactic administration of recombinant human soluble thrombomodulin (rTM) for the prevention of sinusoidal obstruction syndrome (SOS).

MATERIALS AND METHODS

Crl:CD1 mice were allocated to the rTM, placebo, and control groups. The rTM group received an intraperitoneal administration of rTM, with intraperitoneal administration of monocrotaline (MCT) 1 h later. The placebo group received PBS instead of rTM, and the control group received PBS instead of rTM and MCT. Mice were sacrificed 48 h after MCT administration, and blood and liver tissues were evaluated. Immunostaining was performed using anti-CD42b and anti-SE-1 antibodies, and AZAN staining. Levels of plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS) in whole liver tissues were estimated using RT-PCR.

RESULTS

Hematoxylin-eosin staining showed that SOS-related findings were markedly attenuated in the rTM group compared to the placebo group. CD42b immunostaining showed the presence of extravasated platelet activation (EPA) in the Disse space in the placebo group, but this was less noticeable in the rTM group. PAI-1 levels were significantly lower in the rTM group than in the placebo group in RT-PCR. However, eNOS levels were significantly higher in the rTM group than in the placebo group.

CONCLUSION

Administration of rTM may prevent SOS by protecting sinusoidal endothelial cells.

摘要

目的

本研究旨在探讨预防性给予重组人可溶性血栓调节蛋白（rTM）对预防窦状隙阻塞综合征（SOS）的作用。

材料与方法

Crl:CD1 小鼠分为 rTM 组、安慰剂组和对照组。rTM 组给予腹腔内注射 rTM，1 小时后给予腹腔内注射单环酸（MCT）。安慰剂组给予 PBS 代替 rTM，对照组给予 PBS 代替 rTM 和 MCT。MCT 给药后 48 小时处死小鼠，评估血液和肝脏组织。使用抗 CD42b 和抗 SE-1 抗体以及 AZAN 染色进行免疫染色。使用 RT-PCR 估计整个肝组织中纤溶酶原激活物抑制剂（PAI-1）和内皮型一氧化氮合酶（eNOS）的水平。

结果

苏木精-伊红染色显示，与安慰剂组相比，rTM 组 SOS 相关发现明显减轻。CD42b 免疫染色显示，在安慰剂组的 Disse 空间中存在血小板外渗激活（EPA），而 rTM 组则不明显。rTM 组的 PAI-1 水平在 RT-PCR 中明显低于安慰剂组。然而，rTM 组的 eNOS 水平明显高于安慰剂组。