Arterioscl Throm Vas：血栓能感受血流量的变化

2012年10月30日 讯 /生物谷BIOON/ --动脉粥样硬化发病涉及到动脉壁内的脂肪组织，动脉壁上沉积了一层像小米粥样的脂类，使动脉弹性减低、管腔变窄的病变。斑块组织生长，直到动脉壁爆裂，造成动脉内形成血块。这些血栓成长会阻止血液流向冠状动脉，这可能会导致心脏病。

美国宾夕法尼亚大学的一项新研究表明，血栓形成后有意想不到的能力，能意识它周围的血液循环。如果血流速停止，血块感官流量减少，就触发了类似肌肉收缩的现象。收缩挤出水，使血块更加密集。更好地了解凝血动力学以及动脉粥样硬化的发生可能有助开发更有效的药物预防心脏病。

这项研究是由研究生Ryan Muthard和化学和生物分子工程学院工程与应用科学部教授Scott Diamond完成。他们的工作发表在杂志Arteriosclerosis, Thrombosis and Vascular Biology上。

研究人员早已知道试管中的血液凝块后会收缩挤出水。 然而，受伤鼠血管内血栓却观察不到过多收缩活动。采用特殊设计的微流体装置，研究人员用脉冲荧光染料穿过血块调查如何阻止出血。当他们调节阀停止了染料流动，研究人员吃惊地看到，血块中存在一个巨大的收缩。如果他们将保持染料持续流动的话，血块性能没有发生变化。

为了分析上述现象，研究人员利用能结合细胞内钙的荧光染料。他们发现，当流动停止时，血小板的钙水平增加，成为激活状态。加药阻断参与凝血过程的化学物质ADP和血栓素后，研究人员能够防止血小板钙动员和停止收缩。当前，数以百万计的患者服用了针对这些化学途径的药物如：P2Y12抑制剂、氯吡格雷等。研究证实了血栓在心脏病中能感受到血流量的变化。

与血栓相关的拓展阅读：

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• Int J Cardiol：Fontan术后房性心律失常引起大块血栓
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Blood Clots Are Rapidly Assembled Hemodynamic Sensors: Flow Arrest Triggers Intraluminal Thrombus Contraction.

OBJECTIVE: Blood clots form under flow during intravascular thrombosis or vessel leakage. Prevailing hemodynamics influence thrombus structure and may regulate contraction processes. A microfluidic device capable of flowing human blood over a side channel plugged with collagen (±tissue factor) was used to measure thrombus permeability (κ) and contraction at controlled transthrombus pressure drops.

METHODS AND RESULTS: The collagen (κ(collagen)=1.98×10(-11) cm(2)) supported formation of a 20-μm thick platelet layer, which unexpectedly underwent massive platelet retraction on flow arrest. This contraction resulted in a 5.34-fold increase in permeability because of collagen restructuring. Without stopping flow, platelet deposits (no fibrin) had a permeability of κ(platelet)=5.45×10(-14) cm(2) and platelet-fibrin thrombi had κ(thrombus)=2.71×10(-14) cm(2) for ΔP=20.7 to 23.4 mm Hg, the first ever measurements for clots formed under arterial flow (1130 s(-1) wall shear rate). Platelet sensing of flow cessation triggered a 4.6- to 6.5-fold (n=3, P<0.05) increase in contraction rate, which was also observed in a rigid, impermeable parallel-plate microfluidic device. This triggered contraction was blocked by the myosin IIA inhibitor blebbistatin and by inhibitors of thromboxane A2 (TXA(2)) and ADP signaling. In addition, flow arrest triggered platelet intracellular calcium mobilization, which was blocked by TXA(2)/ADP inhibitors. As clots become occlusive or vessels rupture, flow around developed clots diminishes facilitating full platelet retraction and hemostasis.

CONCLUSIONS: Flow dilution of ADP and thromboxane regulates platelet contractility with prevailing hemodynamics, a newly defined flow-sensing mechanism to regulate clot function.