丁酸盐对新生坏死性小肠结肠炎的保护作用及其机制  

Protective effect of butyrate on neonatal necrotizing enterocolitis and its molecular mechanism

作　　者：翟春雨 邢聪 赵冰芳 李志彬[1] 刘雨露[2] Zhai Chunyu;Xing Cong;Zhao Bingfang;Li Zhibin;Liu Yulu(Department of Pediatric General Surgery,the First People’s Hospital of Shangqiu(Clinical College of Xuzhou Medical University),Shangqiu 476000,China;Department of Critical Care Medicine,the First People’s Hospital of Shangqiu(Clinical College of Xuzhou Medical University),Shangqiu 476000,China)

机构地区：[1]商丘市第一人民医院(徐州医科大学临床学院)小儿普外科,商丘476000 [2]商丘市第一人民医院(徐州医科大学临床学院)重症医学科,商丘476000

出　　处：《中华实验外科杂志》2024年第11期2531-2534,共4页Chinese Journal of Experimental Surgery

基　　金：2023年度河南省医学科技攻关计划联合共建项目(IHGI20230980)。

摘　　要：目的:探讨丁酸对新生坏死性小肠结肠炎的保护作用及其分子机制。方法:45只BALB/c新生小鼠按照随机数字表法分为对照组、模型组和丁酸组,每组15只,模型组和丁酸组新生小鼠喂养配方乳灌胃建立坏死性小肠结肠炎模型,对照组新生小鼠进行正常喂养。丁酸组小鼠在出生后3 d灌胃0.05 ml/g丁酸盐溶液,连续治理7 d,对照组和模型组小鼠灌胃等体积生理盐水。建模后3 d处死小鼠,采用苏木精-伊红染色分析3组小鼠结肠组织病理学变化;采用免疫酶联免疫吸附实验分析3组小鼠炎性因子水平变化;采用原位缺口末端标记法(TUNEL)染色分析小鼠结肠组织细胞凋亡水平;采用蛋白质免疫印迹分析结肠组织p38蛋白激酶(p38 MAPK)和核转录因子(NF-κB)亚基p65和p50磷酸化水平变化。组间比较采用单因素方差分析。结果:模型组小鼠体重[(4.87±0.74) g]低于对照组小鼠[(7.27±0.70) g],差异有统计学意义( t=9.081, P<0.05)。丁酸组小鼠体重[(6.07±0.80) g]明显高于模型组[(4.87±0.74) g],差异有统计学意义( t=4.260, P<0.05)。模型组小鼠结肠组织损伤评分[(3.07±0.96)分]高于对照组[(0.67±0.62)分],差异有统计学意义( t=8.138, P<0.05)。丁酸组小鼠结肠组织损伤评分[(1.47±0.51)分]明显低于模型组[(3.07±0.96)分],差异有统计学意义( t=5.679, P<0.05)。丁酸组小鼠结肠组织白细胞介素-1β、肿瘤坏死因子-α、白细胞介素-6和白细胞介素-18[(64.07±11.44)、(54.80±9.37)、(49.20±5.72)、(36.60±5.17) pg/g]明显低于模型组[(138.80±17.72)、(96.47±8.25)、(93.20±12.85)、(82.07±9.50) pg/g],差异有统计学意义( t=13.720、12.930、12.110、16.290, P<0.05)。丁酸组小鼠结肠组织凋亡水平[(7.08±0.60)%]明显低于模型组[(14.51±1.76)%],差异有统计学意义( t=15.510, P<0.05)。丁酸组小鼠结肠组织磷酸化p38 MAPK、磷酸化NF-κB p65、磷酸化NF-κB p50水平(0.68±0.13、0.80±0.09、0.83±0.09)明显低�Objective To investigate the protective effect of butyric acid on neonatal necrotizing enterocolitis and its molecular mechanism.Methods 45 BALB/c newborn mice were divided into control group,model group and butyric acid group according to random number table method,15 mice/per group.The model group and butyric acid group were fed with formula milk to establish necrotic enterocolitis model,while the control group was fed normally.The mice in the butyric acid group were given 0.05 ml/g butyrate solution 3 days after birth and were treated continuously for 7 days.The mice in the control group and the model group were given equal volume normal saline.The mice were killed 3 days after modeling,and the colonic histopathological changes were analyzed by hematoxylin-eosin staining.The levels of inflammatory factors in the three groups were analyzed by enzyme-linked immunosorbent assay.The apoptosis level of colon tissue cells was used to analyze by terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL)staining.The phosphorylation levels of p38 protein kinase(p38 MAPK)and nuclear transcription factor(NF-κB)subunits p65 and p50 in colon tissues were analyzed by Western blotting.One-way analysis of variance was used to compare the measurement data between groups.ResultsThe body weight of mice in the model group[(4.87±0.74)g]was lower than that of the control group[(7.27±0.70)g,t=9.081,P<0.05].The body weight in Butyric acid group[(6.07±0.80)g]significantly lower than the model group mice[(4.87±0.74)g,t=4.260,P<0.05].The colonic tissue injury score of model group[(3.07±0.96)points]was higher than that of control group[(0.67±0.62)points,t=8.138,P<0.05].The colonic tissue damage score of mice in butyric acid group[(1.47±0.51)points]was significantly lower than that in model group[(3.07±0.96)points,t=5.679,P<0.05].Interleukin1β,tumor necrosis factor a,interleukin6 and interleukin18 in colon tissue of mice in butyric acid group[(64.07±11.44),(54.80±9.37),(49.20±5.72),(36.60+5.17)pg/g]significantly

关 键 词：丁酸 新生坏死性小肠结肠炎 P38蛋白激酶 核转录因子 炎症 

分 类 号：R722.1[医药卫生—儿科] R-332[医药卫生—临床医学]