Intestinal NADPH oxidase 2 activity increases in a neonatal rat model of necrotizing enterocolitis.
Intestinal NADPH oxidase 2 activity increases in a neonatal rat model of necrotizing enterocolitis.
复制标题
DOI：
10.1371/journal.pone.0115317
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Gourlay DM
中科院分区：
文献类型：
--
作者：
Welak SR;Rentea RM;Teng RJ;Heinzerling N;Biesterveld B;Liedel JL;Pritchard KA Jr;Fredrich KM;Gourlay DM
坏死性小肠结肠炎（NEC）是早产儿的一种并发症。病因不明，但与肠道喂养、缺血、感染和炎症有关。NEC中活性氧的产生，最明显的是超氧化物，增加。NADPH氧化酶（NOX）产生超氧化物，但其在NEC中的活性仍然未知。我们推测，氮氧化物衍生的超氧化物的生产增加NEC。将新生Sprague-Dawley大鼠分为对照组、配方奶喂养组、配方奶/LPS组、配方奶/缺氧组和NEC组（配方奶、缺氧和LPS）。分析肠匀浆中NADPH依赖性超氧化物的产生。测量第0-4天超氧化物水平的变化。利用一氧化氮合酶（L-NAME）和N 0X 2（GP 91-ds-tat）的抑制剂。RT-PCR检测eNOS、NOX 1、GP 91 phox的表达。免疫荧光研究估计了D1、D2和D4时对照和NEC动物中p47 phox和GP 91 phox的共定位。在D4，NEC幼仔产生的超氧化物多于对照组，而所有其他组均无变化。NADPH依赖的超氧化物的生产是更大的NEC在第0，3和4天。GP 91-ds-tat降低了两组中超氧化物的产生，在NEC中具有更大的抑制作用。L-NAME不改变超氧化物的产生。时间上，超氧化物的生产变化最小的控制。在NEC中，超氧化物生成在第1天减少，但在第3-4天增加。GP 91 phox在NEC中的表达在第2天和第4天更高。NOX 1和eNOS表达与对照组相比无变化。在D1和D2，GP 91 phox和p47 phox在所有对照样品和NEC样品中具有最小的共定位，但在D4具有增加的共定位。总之，这项研究证明，实验诱导的NEC增加小肠NOX活性。NEC模型的所有组件都是增加NOX活性所必需的。NOX 2是主要来源，特别是随着疾病的进展。
Necrotizing enterocolitis (NEC) is a complication of prematurity. The etiology is unknown, but is related to enteral feeding, ischemia, infection, and inflammation. Reactive oxygen species production, most notably superoxide, increases in NEC. NADPH oxidase (NOX) generates superoxide, but its activity in NEC remains unknown. We hypothesize that NOX-derived superoxide production increases in NEC. Newborn Sprague-Dawley rats were divided into control, formula-fed, formula/LPS, formula/hypoxia, and NEC (formula, hypoxia, and LPS). Intestinal homogenates were analyzed for NADPH-dependent superoxide production. Changes in superoxide levels on days 0-4 were measured. Inhibitors for nitric oxide synthase (L-NAME) and NOX2 (GP91-ds-tat) were utilized. RT-PCR for eNOS, NOX1, GP91phox expression was performed. Immunofluorescence studies estimated the co-localization of p47phox and GP91phox in control and NEC animals on D1, D2, and D4. NEC pups generated more superoxide than controls on D4, while all other groups were unchanged. NADPH-dependent superoxide production was greater in NEC on days 0, 3, and 4. GP91-ds-tat decreased superoxide production in both groups, with greater inhibition in NEC. L-NAME did not alter superoxide production. Temporally, superoxide production varied minimally in controls. In NEC, superoxide generation was decreased on day 1, but increased on days 3-4. GP91phox expression was higher in NEC on days 2 and 4. NOX1 and eNOS expression were unchanged from controls. GP91phox and p47phox had minimal co-localization in all control samples and NEC samples on D1 and D2, but had increased co-localization on D4. In conclusion, this study proves that experimentally-induced NEC increases small intestinal NOX activity. All components of NEC model are necessary for increased NOX activity. NOX2 is the major source, especially as the disease progresses.
登录
查看更多内容
影响因子：
8.3
作者：
Li, JM;Gall, NP;Shah, AM
通讯作者：
Shah, AM
影响因子：
20.1
作者：
GRIENDLING, KK;MINIERI, CA;ALEXANDER, RW
通讯作者：
ALEXANDER, RW
DOI：
10.1007/s10024-002-0602-z
发表时间：
2003-01
期刊：
Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
影响因子：
--
作者：
Hsueh W;Caplan MS;Qu XW;Tan XD;De Plaen IG;Gonzalez-Crussi F
通讯作者：
Gonzalez-Crussi F
影响因子：
20.1
作者：
Lassègue B;San Martín A;Griendling KK
通讯作者：
Griendling KK
影响因子：
20.1
作者：
Lassègue, B;Sorescu, D;Griendling, KK
通讯作者：
Griendling, KK