Miele Lino F, Turhan Aslihan, Lee Grace S, Lin Miao, Ravnic Dino, Tsuda Akira, Konerding Moritz A, Mentzer Steven J
Laboratory of Adaptive and Regenerative Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Anat Rec (Hoboken). 2009 Aug;292(8):1143-53. doi: 10.1002/ar.20954.
In the normal murine mucosal plexus, blood flow is generally smooth and continuous. In inflammatory conditions, such as chemically-induced murine colitis, the mucosal plexus demonstrates markedly abnormal flow patterns. The inflamed mucosal plexus is associated with widely variable blood flow velocity as well as discontinuous and even bidirectional flow. To investigate the mechanisms responsible for these blood flow patterns, we used intravital microscopic examination of blood flow within the murine mucosal plexus during dextran sodium sulphate-and trinitrobenzenesulfonic acid-induced colitis. The blood flow patterns within the mucosal plexus demonstrated flow exclusion in 18% of the vessel segments (P < 0.01). Associated with these segmental exclusions was significant variation in neighboring flow velocities. Intravascular injection of fluorescent platelets demonstrated platelet incorporation into both fixed and rolling platelet aggregates. Rolling platelet aggregates (mean velocity 113 microm/sec; range, 14-186 microm/sec) were associated with reversible occlusions and flow variations within the mucosal plexus. Gene expression profiles of microdissected mucosal plexus demonstrated enhanced expression of genes for CCL3, CXCL1, CCL2, CXCL5, CCL7, CCL8, and Il-1b (P < 0.01), and decreased expression of CCL6 (P < 0.01). These results suggest that platelet aggregation, activated by the inflammatory mileau, contributes to the complex flow dynamics observed in acute murine colitis.
在正常小鼠黏膜丛中，血流通常是平稳且连续的。在炎症状态下，如化学诱导的小鼠结肠炎，黏膜丛会呈现出明显异常的血流模式。发炎的黏膜丛与血流速度广泛变化以及血流不连续甚至双向流动有关。为了研究这些血流模式的形成机制，我们在葡聚糖硫酸钠和三硝基苯磺酸诱导的结肠炎期间，对小鼠黏膜丛内的血流进行了活体显微镜检查。黏膜丛内的血流模式显示，18%的血管段出现血流受阻（P < 0.01）。与这些节段性受阻相关的是相邻血流速度的显著变化。血管内注射荧光标记的血小板显示，血小板融入了固定和滚动的血小板聚集体中。滚动的血小板聚集体（平均速度113微米/秒；范围为14 - 186微米/秒）与黏膜丛内的可逆性阻塞和血流变化有关。显微解剖的黏膜丛的基因表达谱显示，CCL3、CXCL1、CCL2、CXCL5、CCL7、CCL8和Il-1b基因的表达增强（P < 0.01），而CCL6基因的表达降低（P < 0.01）。这些结果表明，由炎症环境激活的血小板聚集，促成了急性小鼠结肠炎中观察到的复杂血流动力学变化。
