Endothelin-1 in human intestine resected for necrotizing enterocolitis
Endothelin-1 in human intestine resected for necrotizing enterocolitis
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DOI：
10.1016/j.jpeds.2005.01.046
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发表时间：
2005-06-01
影响因子：
5.1
通讯作者：
Caniano, DA
中科院分区：
文献类型：
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作者：
Nowicki, PT;Dunaway, DJ;Caniano, DA
目的：我们询问，与同一切除标本中相对健康的区域相比，具有坏死性小肠结肠炎（NEC）组织学证据的早产儿肠道区域中强效血管收缩剂内皮素-1 （ET-1）的组织浓度是否更高。然后，我们评估ET-1是否参与肠浆膜下小动脉内的血流动力学调节，这些小动脉取材于人类早产儿小肠的NEC部分。研究设计：根据与穿孔的距离将切除的NEC早产儿肠分为三个区域（1区最近，3区最远）。在每个区域进行NEC的组织学检查（正常= 0，晚期坏死= 6）。采用酶联免疫吸附法测定各区肠道匀浆中ET-1的组织浓度。对不同区域的浆膜下小动脉进行体外血流动力学测定。在压力梯度（AP）为20和40 mmHg的控制条件下，以及用BQ610 （10(-9)mol/L）阻断内皮素- ETA受体后，分别测定小动脉流速、直径和阻力。结果3个区ET-1组织浓度（pg/mg蛋白）和组织学评分分别为：1区84 14、5.5 +/- 0.3；2区分别为99 +/- 12、4.7 +/- 0.4和3:33 +/- 9、0.8 +/- 0.6 （M +/- SD, n = 10个切除标本，P < 0.05, 3区vs 1区和2区）。当AP为20或40 mmHg时，对照条件下2区小动脉流速和直径明显低于3区小动脉，阻力明显增加（P < 0.05）。BQ610对第3区小动脉无影响，但对第2区小动脉有明显扩张作用，血流速率和血管直径增加，血管阻力降低（n = 7, P < 0.05）。结论ET-1在早产儿肠组织中浓度较高，具有N-EC的组织学依据。与同一切除标本中相对健康的小肠小动脉相比，切除前肠的小动脉表现出NEC的组织学证据，血管收缩。这种血管收缩可通过阻断内皮素- ETA受体而逆转。
Objectives We asked if the tissue concentration of the potent vasoconstrictor endothelin-1 (ET-1) is greater in areas of human preterm intestine that demonstrate histologic evidence of necrotizing enterocolitis (NEC) when compared with relatively healthy areas within the same resection specimen. We then evaluated if ET-1 participates in hemodynamic regulation within intestinal subserosal arterioles harvested from portions of human preterm intestine that demonstrate NEC.Study design Human preterm intestine resected for NEC was divided into three zones based on proximity to the perforation (zone 1 most proximal, zone 3 most distal). Histologic evidence of NEC was determined in each zone (normal = 0, advanced necrosis = 6). The tissue concentration of ET-1 was determined by enzyme-linked immunosorbent assay within intestinal homogenates prepared from each zone. Arteriolar hemodynamics were determined in vitro on subserosal arterioles harvested from different zones. Arteriolar flow rate, diameter, and resistance were determined at pressure gradients (AP) of 20 and 40 mmHg under control conditions and again after blockade of endothelin ETA receptors with BQ610 (10(-9)mol/L).Results The tissue concentration of ET-1 (pg/mg protein) and histologic score in the three zones were: zone 1: 84 14, 5.5 +/- 0.3; zone 2: 99 +/- 12, 4.7 +/- 0.4, and zone 3:33 +/- 9, 0.8 +/- 0.6, respectively (M +/- SD, n = 10 resection specimens, P < .05, zone 3 vs zones I and 2). Zone 2 arterioles demonstrated significantly lower flow rate and diameter and increased resistance under control conditions than zone 3 arterioles when AP was either 20 or 40 mmHg (it = 7, P < .05). Treatment with BQ610 had no effect on zone 3 arterioles but significantly vasodilated zone 2 arterioles, increasing flow rate and vessel diameter, and decreasing vascular resistance (n = 7, P < .05).Conclusions The tissue concentration of ET-1 is greater in human preterm intestine that demonstrates histologic evidence of N-EC. Arterioles harvested front intestine exhibiting histologic evidence of NEC demonstrate vasoconstriction when compared with arterioles from relatively healthy intestine in the same resection specimen. This vasoconstriction was reversed by blockade of endothelin ETA receptors.