Henke Peter K, Varma Manu R, Deatrick K Barry, Dewyer Nicholas A, Lynch Erin M, Moore Andrea J, Dubay Derek A, Sukheepod Pasu, Pearce Charles G, Upchurch Gilbert R, Kunkel Steven L, Franz Michael G, Wakefield Thomas W
University of Michigan Health System, 1500 E. Medical Center Drive, 2210 Taubman Health Care Center, Ann Arbor, MI 48109-0329 USA.
Thromb Haemost. 2006 Feb;95(2):272-81. doi: 10.1160/TH05-02-0099.
Early deep venous thrombosis (DVT) resolution is associated with neutrophil (PMN) influx. This study examined the role of PMNs in thrombus neovascularization and vein wall injury after DVT. A rat model of DVT by inferior vena cava (IVC) ligation was performed with control serum or rabbit anti-rat PMN serum administered perioperatively with sacrifice at 2 and 7 days. At 2 days, neutropenic rats had 1.6-fold larger thrombi (P = .04) and 1.4-fold higher femoral venous pressures by water manometry (P = .008) but no difference in thrombus neovascularization was observed. By 7 days, DVT sizes were similar, but vein wall injury persisted in the neutropenic rats with a 2.0-fold increase in vein wall stiffness by microtensiometry (P < .05), as well as a 1.2-fold increased thickness (P = .04). Collagen and profibrotic growth factors were significantly increased in neutropenic IVC at 7 days (all P < .05). Vein wall and intrathrombus uPA byWestern immunoblotting, and intrathrombus MMP-9 gelatinase activity were significantly less in neutropenic rats than controls (P < .001). Conversely, MMP-2 was significantly elevated in neutropenic IVC at 2 days after DVT. However, neutropenia induced 24 hours after DVT formation resulted in no significant increase in vein wall stiffness or collagen levels at 7 days, despite 1.4-fold larger thrombi (P < .05). These data suggest a critical early role for PMN in post DVT vein wall remodeling.
早期深静脉血栓形成（DVT）的溶解与中性粒细胞（PMN）的流入有关。本研究探讨了PMN在DVT后血栓新生血管形成和静脉壁损伤中的作用。通过下腔静脉（IVC）结扎建立大鼠DVT模型，在围手术期给予对照血清或兔抗大鼠PMN血清，并在第2天和第7天处死。在第2天，中性粒细胞减少的大鼠血栓体积增大1.6倍（P = 0.04），通过水柱测压法测得股静脉压力升高1.4倍（P = 0.008），但未观察到血栓新生血管形成有差异。到第7天，DVT大小相似，但中性粒细胞减少的大鼠静脉壁损伤持续存在，通过微张力测定法测得静脉壁硬度增加2.0倍（P < 0.05），厚度增加1.2倍（P = 0.04）。在第7天，中性粒细胞减少的IVC中胶原蛋白和促纤维化生长因子显著增加（均P < 0.05）。通过Western免疫印迹法检测，中性粒细胞减少的大鼠静脉壁和血栓内的尿激酶型纤溶酶原激活剂（uPA）以及血栓内基质金属蛋白酶-9（MMP-9）的明胶酶活性显著低于对照组（P < 0.001）。相反，在DVT后第2天，中性粒细胞减少的IVC中MMP-2显著升高。然而，在DVT形成后24小时诱导的中性粒细胞减少，尽管血栓体积增大1.4倍（P < 0.05），但在第7天时静脉壁硬度或胶原蛋白水平没有显著增加。这些数据表明PMN在DVT后静脉壁重塑中起关键的早期作用。
