P-selectin inhibition decreases post-thrombotic vein wall fibrosis in a rat model
P-selectin inhibition decreases post-thrombotic vein wall fibrosis in a rat model
复制标题
DOI：
10.1067/msy.2003.249
复制
发表时间：
2003-08-01
期刊：
影响因子：
3.8
通讯作者：
Henke, PK
中科院分区：
文献类型：
--
作者：
Thanaporn, P;Myers, DD;Henke, PK
背景。深静脉血栓形成（DVT）后静脉功能不全是一个令人烦恼的问题，尽管有有效的抗凝治疗，其特征是静脉壁纤维化。本研究验证了p -选择素抑制可减少血栓后静脉壁纤维化和相关促纤维化介质的假设。采用大鼠深静脉血栓瘀阻模型制备2 d深静脉血栓。然后大鼠静脉注射生理盐水（对照组），rPSGL-Ig （4 mg/kg）一次，或每天皮下注射低分子肝素（0.5 mg/kg）。治疗7天后取下腔静脉壁，观察血栓大小；白细胞内容;酶联免疫吸附法检测促纤维化介质半定量实时聚合酶链反应法表达ⅰ型和ⅲ型胶原mRNA；和胶原蛋白。两组间血栓块和白细胞计数相似。rPSGL-Ig和低分子肝素治疗后，静脉壁胶原蛋白减少（P < 0.05）。rPSGL-Ig治疗（以及低分子肝素的类似趋势）与纤维化介质减少相关，包括IL-13、MCP-1、bFGH和转化生长因子- β减少（P < 0.05）。低分子肝素组胶原蛋白III基因表达升高，ⅰ型胶原基因表达不升高（P < 0.05）。用rPSGL-Ig或低分子肝素抑制p -选择素可减少dvt后静脉壁纤维化，并与静脉壁促纤维化介质减少有关。这种作用与血栓块和静脉壁白细胞无关。
Background. Post-deep vein thrombosis (DVT) venous insufficiency is a vexing problem despite effective anticoagulation, and is characterized by vein wall fibrosis. This study tested the hypothesis that P-selectin inhibition would decrease post-thrombotic vein wall fibrosis and associated profibrotic mediators.Methods. A rat stasis model of DVT was used to produce a 2-day-old DVT. Rats then received either intravenous saline (control), rPSGL-Ig (4 mg/kg) once, or daily subcutaneous low molecular weight heparin (LMWH) (0.5 mg/kg). Inferior vena cava wall was harvested 7 days after treatment and processed for thrombus size; leukocyte content; profibrotic mediators by enzyme-linked immunosorbent assay; collagen I and III mRNA expression by semiquantitative real-time polymerase chain reaction; and for collagen protein.Results. Thrombus mass and leukocyte counts were similar between the groups. Treatment with rPSGL-Ig and LMWH resulted in less vein wall collagen (P < .05). rPSGL-Ig treatment (and a similar trend for LMWH) was associated with decreased profibrotic mediators, including less IL-13, MCP-1, bFGH, and transforming growth factor-beta (P < .05). Clollagen III gene expression, but not collagen I gene expression, was increased with LMWH treatment (P < .05).P-selectin inhibition with rPSGL-Ig or LMWH decreases post-DVT vein wall fibrosis, and is associated with decreased vein wall profibrotic mediators. This effect is independent of thrombus mass and vein wall leukocytes.