摘要
目的评价重组人β防御素3（recombinant human beta-defensin-3，rhBD3）对新生大鼠坏死性小肠结肠炎（NEC）模型的干预作用。方法采用人工喂养联合缺氧及冷刺激方法制备新生SD大鼠NEC模型。实验分组：A组为正常组（12只），B组为正常rhBD3干预组（12只），C组为NEC模型组（20只），D组为NEC模型rhBD3干预组（24只）。收集肠管和血液标本。结果①rhBD3对正常新生大鼠无明显影响，但能够维持NEC模型大鼠的体质量（出生后第四天，P=0．015），降低NEC发病率（P=0．039），提高生存率（P〈0．001），改善NEC疾病的严重程度（P=0．01）；②rhBD3可以降低肠壁和血清中炎症因子IL-6和TNF-α的表达；③rhBD3增加血清中二胺氧化酶（diamine oxidase，DA0）的水平，并增加紧密连接蛋白ZO-1的表达。结论经胃管给予rhBD3对新生大鼠NEC模型具有一定的保护作用，其作用可能与降低肠壁组织中炎症水平以及保持肠壁黏膜完整性有关。
Objective To evaluate the beneficial effects of recombinant human beta-defensin-3 （rhBD3） in neonatal rats with necrotizing enterocolitis （NEC）. Methods A total of 68 newborn Sprague-Dawley rats were randomly divided into 4 groups of control （n = 12）, control ＋ rhBD3 （n = 12）, NEC （n = 20） and NEC ＋ rhBD3 （n = 24）. The former two groups were maternally fed. Experimental NEC was induced by the exposures to hypertonic feeding, asphyxia and hypothermia. And rhBD3 （100 μg/kg with a daily volume of 0. 1 ml） was administered via a gastric tube. Body weight, histologicalscore, survival time, cytokine expression and mucosal integrity were evaluated. Results The group NEC ＋ hBD3maintained body weight. And rhBD3 dosing decreased the incidence of NEC from 80% in group NEC to 50% in group NEC＋ hBD3 （P = 0. 039）, boosted the survival rate from 25% in group NEC to 62. 5% in group NEC ＋ hBD3 （P〈0. 001） and reduced the severity of NEC （mean NEC scores： 2. 50 and 1.67 respectively, P = 0. 01）. Moreover, rhBD3 reduced the expressions of pro-inflammatory cytokines （TNF-alpha, IL-6） in ileum and sera. And the serum level of diamine oxidase （DAO） and the expression of ZO-1 were also evaluated. Decreased DAO activity was detected in group NEC. And rhBD3 treatment increased the serum concentration of DAO and up- regulated the expression of ZO-1. Conclusions rhBD3 protects newborn rats from NEC due to lower levels of inflammatory mediators and preserved mucosal integrity.
出处
《中华小儿外科杂志》
CSCD
2015年第2期109-112,共4页
Chinese Journal of Pediatric Surgery
基金
上海市科委课题（124119a6500）
国家自然科学基金（81370743）
上海市小儿消化与营养重点实验室（11DZ2260500）
