解放军医学杂志2018，Vol.43Issue(3)：201-205,5.DOI:10.11855/j.issn.0577-7402.2018.03.04
丁酸对新生儿坏死性小肠结肠炎新生小鼠模型的保护作用
Protective effect of sodium butyrate on the neonatal mouse model of necrotizing enterocolitis
摘要
Abstract
Objective To investigate the protective effect of sodium butyrate on the neonatal mouse model of necrotizing enterocolitis and analyze its possible mechanism.Methods Sixty c57BL/6 neonatal mice were randomly divided into two groups (n=30):PBS group and butyric acid group.At the third day after birth,mice in both groups were respectively given PBS and sodium butyrate solution by gavage once a day for 7 days,and neonatal necrotizing enterocolitis (NEC) model was established by hypoxia,cold stimulation and artificial feeding.The newborn mice were sacrificed overnight after modeling.HE staining and double-blind pathological score were performed to observe the pathological changes of ileocecal intestinal tissue.The mRNA expressions of IL-6,IL-10,TGF-β1 and TNF-a were tested by quantitative real-time PCR.The levels of IL-10 and TGF-β1 in intestine tissues were evaluated using ELISA.Flow cytometry was used to analyze the ratio of regulatory T cells (Treg) on CD4+ T cells in both groups.Results When mice were sacrificed overnight after NEC modeling,the body weight was significantly higher in butyric acid group (4.50 ± 0.42g) than in PBS group (4.16 ± 0.60g,P＜0.05);No significant difference (P＞0.05) existed in survival rate of butyric acid group (76.34％) and PBS group (67.95％).The pathological damage score of intestinal tissue showed that the median score of intestinal injury was significantly lower in butyric acid group [1.33(1.33-1.67)] than in PBS group [2.00(1.67-2.25),P＜0.05].qPCR demonstrated that the expressions of IL-6 and TNF-α mRNA were obviously lower in butyric acid group than in PBS group (0.85 ± 0.30 vs.1.77 ± 0.49 and 0.41 ± 0.25 vs.0.96 ± 0.56,respectively,P＜0.05);and the expressions of IL-10 and TGF-β1 mRNA were markedly higher in butyric acid group than in PBS group (1.91 ± 0.82 vs.0.94 ± 0.43 and 1.46 ± 0.57 vs.0.88 ± 0.29,respectively,P＜0.05);Intestinal tissue ELISA results showed that the expressions of IL-10 and TGF-β1 were higher in butyric acid group than in PBS group (68.60 ± 15.06 vs.37.25 ± 5.81 and 424.93 ± 19.34 vs.127.31 ± 60.83,respectively,P＜0.05);Flow cytometry revealed that the proportion of regulatory T cells (Treg) of CD4+ T cells was higher in butyric acid group than in PBS group (12.68％ ± 6.79％ vs.3.57％ ± 0.88％,P＜0.05).Conclusions Butyric acid plays a protective effect in the intestinal injury of neonatal mouse model of necrotizing enterocolitis.The possible mechanism is that butyrate can down-regulate the expressions of cytokines IL-6 and TNF-o,up-regulate the expressions of cytokines IL-10 and TGF-β1,and promote the differentiation of T cells into Treg cells.关键词
丁酸/新生儿坏死性小肠结肠炎/白细胞介素-10/转化生长因子-β1/调节性T细胞Key words
butyric acid/neonatal necrotizing enterocolitis/interleukin-10/transforming growth factor-β1/regulatory T cell分类
医药卫生引用本文复制引用
李秋平,余加林,胡坤,贺雨,肖洒,侯婷,艾青..丁酸对新生儿坏死性小肠结肠炎新生小鼠模型的保护作用[J].解放军医学杂志,2018,43(3):201-205,5.基金项目
国家自然科学基金(81571483) （81571483）
儿童医院临床研究项目[(2014)254-1cyj2014-11]This work was supported by the National Natural Science Foundation of China (81571483) （2014）
the Clinical Research Foundation of Children's Hospital of Chongqing Medical University [(2014)254-1cyj2014-11] （2014）
