An Animal Model of Necrotizing Enterocolitis (NEC) in Preterm Rabbits
An Animal Model of Necrotizing Enterocolitis (NEC) in Preterm Rabbits
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DOI：
10.3109/15513815.2012.681426
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发表时间：
2013-01-01
影响因子：
1.1
通讯作者：
Smith, Samuel D.
中科院分区：
文献类型：
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作者：
Bozeman, Andrew P.;Dassinger, Melvin S.;Smith, Samuel D.
建立一个坏死性小肠结肠炎（NEC）的动物模型，允许调整的严重程度和潜在的可恢复性是必要的，以研究预防和治疗策略的有效性。本研究描述了一种能够调节NEC样组织学变化严重程度的早产兔新模型。早产2天通过剖腹产分娩幼兔（n = 151）。在治疗组中，将组织粘合剂应用于肛门开口，以模拟早产儿的肠功能差和运动障碍。根据肛门阻塞类型和处死的生命天数的差异，将幼仔分为5组：3 INT（3天间歇性阻滞）、4 INT（4天间歇性阻滞）、3COM（3天完全阻滞）、4COM（4天完全阻滞）。第五组，4CON，包括对照组（n = 28），无肛门阻滞，在第4天处死受试者。所有幼鼠均灌胃喂食被阴沟肠杆菌、雷尼替丁和吲哚美辛污染的配方奶粉。处死后，收获肠以获得NEC的病理学证据。设盲的病理学家使用0-4级量表对与NEC一致的组织学变化进行分级，其中4级为最严重。研究组中57只幼仔（57/123）（46%）存活至处死，而对照组中26/28只（93%）存活至处死，p < 0.0001。NEC样损伤的发生率和严重程度随着肛门阻塞的持续时间和完全性而增加。44/57（77%）的存活者显示不同程度的大肠和小肠NEC样损伤，3/26（12%）分别在研究组和对照组中显示早期NEC样粘膜损伤。该动物模型在早产兔的小肠和大肠中产生NEC样病理变化。由于损伤的发生率和严重程度随着肠动力障碍的持续时间和完整性而增加，这使得未来的非手术治疗和预防NEC的有效性研究成为可能。
Creation of an animal model of necrotizing enterocolitis (NEC) allowing adjustment of severity and potential recoverability is needed to study effectiveness of prevention and treatment strategies. This study describes a novel model in preterm rabbits capable of adjusting severity of NEC-like histologic changes. Rabbit pups (n = 151) were delivered by cesarean section 2 days preterm. In the treatment groups, tissue adhesive was applied to anal openings to simulate the poor intestinal function and dysmotility of preterm neonates. Pups were placed into five groups: 3INT (3 day intermittent block), 4INT (4 day intermittent block), 3COM (3 day complete block), 4COM (4 day complete block), based on differences in type of anal blockage and day of life sacrificed. The fifth group, 4CON, was comprised of a control arm (n = 28) without anal block, with sacrifice of subjects on day 4. All pups were gavage fed with formula contaminated with Enterobacter cloacae, ranitidine, and indomethacin. Following sacrifice, the intestines were harvested for pathologic evidence of NEC. A blinded pathologist graded histologic changes consistent with NEC using a grading scale 0-4 with 4 being most severe. Fifty-seven pups (57/123) (46%) in the research arm survived to sacrifice, compared to 26/28 (93%) in the control arm of the investigation, p < 0.0001. The incidence and severity of NEC-like damage increased with the duration and completeness of the anal blockage. 44/57 (77%) of survivors revealed various degrees of NEC-like damage to large and small bowel, and 3/26 (12%) exhibited early NEC-like mucosal injury in the research and control arms, respectively. This animal model produces NEC-like pathologic changes in both small and large intestine in preterm rabbits. Because incidence and severity of damage increases with duration and completeness of intestinal dysmotility, this allows future effectiveness studies for nonsurgical treatment and prevention of NEC.