Protective effect of sodium butyrate on the neonatal mouse model of necrotizing enterocolitis
10.11855/j.issn.0577-7402.2018.03.04
- VernacularTitle: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
- Author:
Qiu-Ping LI
1
;
Jia-Lin YU
;
Kun HU
;
Yu HE
;
Sa XIAO
;
Ting HOU
;
Qing AI
Author Information
1. 400014,重庆 重庆医科大学附属儿童医院新生儿科、儿童发育疾病研究教育部重点实验室、儿科学重庆市重点实验室、儿童发育重大疾病国家国际科技合作基地
- Keywords:
butyric acid;
neonatal necrotizing enterocolitis;
interleukin-10;
transforming growth factor-β1;
regulatory T cell
- From:
Medical Journal of Chinese People's Liberation Army
2018;43(3):201-205
- CountryChina
- Language:Chinese
-
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.
