Harris Norman R, Whatley Joseph R, Carter Patsy R, Specian Robert D
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Inflamm Bowel Dis. 2005 Sep;11(9):806-13. doi: 10.1097/01.mib.0000178262.95980.65.
Leukocyte and platelet adherence in postcapillary venules has been speculated to induce constriction of closely paired arterioles. This mechanism was investigated in the current study, in a model of intestinal inflammation induced by dextran sodium sulfate (DSS; 5,000 molecular weight).
Closely paired, parallel arterioles and venules in the submucosa of the mouse intestine were observed using fluorescent intravital microscopy. Arterioles in control mice were compared to arterioles in mice given 5% DSS in drinking water for 11 days.
DSS induced an inflammatory response in which fluorescently labeled leukocytes and platelets were observed adhering to venules. Arterioles constricted and flow decreased significantly when the arterioles were paired with venules having adherent leukocytes and platelets, although the decreases in flow and diameter appeared to be more dependent on platelet than leukocyte adherence. No significant constriction was observed in arterioles paired with venules having minimal platelet adherence. Inhibition of thromboxane with 100 mg/kg ozagrel induced a significant dilation of arterioles in DSS mice that was absent in control mice.
The results are consistent with a proposed mechanism in which thromboxane constricts submucosal arterioles when the arterioles are closely paired with platelet-bearing venules in DSS-induced inflammation.
推测毛细血管后微静脉中的白细胞和血小板黏附会导致紧密配对的小动脉收缩。在本研究中,在右旋糖酐硫酸钠(DSS;分子量5000)诱导的肠道炎症模型中对该机制进行了研究。
使用荧光活体显微镜观察小鼠肠道黏膜下层紧密配对的平行小动脉和微静脉。将对照小鼠的小动脉与饮用含5% DSS的水11天的小鼠的小动脉进行比较。
DSS诱导了一种炎症反应,观察到荧光标记的白细胞和血小板黏附于微静脉。当小动脉与有白细胞和血小板黏附的微静脉配对时,小动脉收缩且血流显著减少,尽管血流和直径的减少似乎更多地依赖于血小板而非白细胞的黏附。在与血小板黏附极少的微静脉配对的小动脉中未观察到明显收缩。用100 mg/kg奥扎格雷抑制血栓素可使DSS小鼠的小动脉显著扩张,而对照小鼠则无此现象。
结果与一种推测机制相符,即在DSS诱导的炎症中,当小动脉与含血小板的微静脉紧密配对时,血栓素会使黏膜下小动脉收缩。