Lee Seungjun, Carter Patsy R, Watts Megan N, Bao Jianxiong R, Harris Norman R
Department of Molecular & Cellular Physiology, Louisiana State University Health Sciences Center in Shreveport, Shreveport, Louisiana 71130, USA.
Inflamm Bowel Dis. 2009 Jul;15(7):1007-13. doi: 10.1002/ibd.20877.
Ingestion by mice of dextran sodium sulfate (DSS) induces colonic vasoconstriction and inflammation, with some of the effects potentially mediated by the vasoconstrictor endothelin-1 (ET-1).
In this study, mice given 5% 40 kD DSS for 5-6 days had elevated colonic immunostaining for ET-1 and platelet endothelial cell adhesion molecule-1 (PECAM-1). Increased ET-1 can induce microvascular constriction; however, the increase in PECAM-1 is consistent with angiogenesis that could decrease flow resistance.
Our measurements of intestinal blood flow, via infused microspheres, suggests that these 2 factors may offset each other, with only a nonsignificant tendency for a DSS-induced decrease in flow. Daily administration of the endothelin converting enzyme inhibitor SM-19712 (15 mg/kg) attenuated DSS-induced increases in colonic immunostaining of ET-1 and PECAM-1.
SM-19712 attenuated histologic signs of tissue injury and inflammation induced by DSS, and decreased the extent of loose stools and fecal blood. However, the inhibitor did not significantly decrease DSS-induced colon shortening or tissue levels of myeloperoxidase (an indicator of neutrophil infiltration).
给小鼠喂食葡聚糖硫酸钠（DSS）可诱导结肠血管收缩和炎症，其中一些效应可能由血管收缩剂内皮素-1（ET-1）介导。
在本研究中，给予5% 40 kD DSS 5 - 6天的小鼠结肠中ET-1和血小板内皮细胞黏附分子-1（PECAM-1）的免疫染色升高。ET-1增加可诱导微血管收缩；然而，PECAM-1增加与可降低血流阻力的血管生成一致。
我们通过注入微球对肠血流量的测量表明，这两个因素可能相互抵消，DSS诱导的血流量减少仅呈不显著趋势。每日给予内皮素转换酶抑制剂SM-19712（15 mg/kg）可减弱DSS诱导的结肠ET-1和PECAM-1免疫染色增加。
SM-19712减轻了DSS诱导的组织损伤和炎症的组织学征象，并减少了稀便和便血的程度。然而，该抑制剂并未显著降低DSS诱导的结肠缩短或髓过氧化物酶的组织水平（中性粒细胞浸润的指标）。
