补充牛乳铁蛋白对早产鼠坏死性小肠结肠炎肠道炎性因子表达的影响  

Effect of bovine lactoferrin supplementation on intestinal inflammatory factor expression in premature rats model of necrotizing enterocolitis

作　　者：孔祥永 庄璐 王梅玉 张珊[1] 彭健茹 封志纯 Kong Xiangyong;Zhuang Lu;Wang Meiyu;Zhang Shan;Peng Jianru;Feng Zhichun(NICU for Very Preterm Infants,Affiliated Bayi Children′s Hospital,the 7^th Medical Center of the Chinese People′s Liberation Army General Hospital,Beijing Key Laboratory of Pediatric Organ Failure,National Engineering Laboratory for Birth Defects Prevention and Control of Key Technology,Clinical Medical College,the 7^th Medical Center of the Chinese People′s Liberation Army General Hospital,Southern Medical University,Beijing 100700,China)

机构地区：[1]解放军总医院第七医学中心附属八一儿童医院极早产NICU,儿童器官功能衰竭北京市重点实验室,出生缺陷防控关键技术国家工程实验室,南方医科大学解放军总医院第七医学中心临床医学院,北京100700

出　　处：《中华实用儿科临床杂志》2020年第2期151-155,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金面上项目(81471492)。

摘　　要：目的探讨补充牛乳铁蛋白(bLF)对早产大鼠坏死性小肠结肠炎(NEC)模型肠道黏膜组织的保护作用及对炎性因子表达的影响,为补充bLF预防NEC提供理论依据。方法SD早产大鼠随机分为4组,每组25只。对照组:单纯人工喂养;模型组:人工喂养+脂多糖(LPS)灌胃+缺氧刺激;高剂量bLF干预组:每天给予bLF(7g/L)+人工喂养+LPS灌胃+缺氧刺激;低剂量bLF干预组:每天给予bLF(2 g/L)+人工喂养+LPS灌胃+缺氧刺激。应用HE染色进行组织病理学分析。酶联免疫吸附法(ELISA)检测肠道黏膜组织白细胞介素(IL)-1β和IL-6的表达水平。结果(1)形态学观察:模型组大鼠肠壁菲薄,肠腔可见不同程度积气、积液。镜下见肠道组织坏死严重,肠壁绒毛脱落,腺体排列紊乱,上皮细胞水肿明显,固有层和黏膜下层重度水肿、分离,大量炎性细胞浸润。高剂量bLF干预组和低剂量bLF干预组大鼠上述表现减轻,对照组无明显异常。(2)肠道组织炎性因子IL-1β、IL-6的表达:模型组大鼠肠道黏膜组织中IL-1β和IL-6的表达水平[(380.89±20.25)ng/L,(485.12±31.44)ng/L]均高于对照组[(270.69±45.58)ng/L,(212.62±89.46)ng/L],差异均有统计学意义(q=9.785、14.030,均P<0.01)。缺氧和LPS刺激大鼠经过bLF喂养,回肠黏膜组织中IL-1β和IL-6的表达被显著抑制,差异均有统计学意义(IL-1β:q=9.105、8.761,均P<0.01;IL-6:q=8.175、8.996,均P<0.01)。高剂量bLF干预组与低剂量bLF干预组IL-1β和IL-6的表达差异均无统计学意义(IL-1β:q=-0.084,P>0.05;IL-6:q=-1.140,P>0.05)。结论经肠道补充bLF可减轻早产SD大鼠NEC模型肠道组织的损伤程度,并抑制肠道组织IL-1β和IL-6炎性因子的表达,对早产SD大鼠肠道组织有一定的保护作用。Objective To investigate the protective effects of bovine lactoferrin(bLF)supplementation on intestinal mucosal tissue and its influence on of inflammatory factors in the premature rats model of necrotizing enterocolitis(NEC),and to provide the theoretical basis for prevention of NEC by bLF supplementation.Methods Premature SD rats were randomly divided into 4 groups,25 cases in each group.Control group:oral feeding;model group:oral feeding with lipopolysaccharides(LPS)gavage+hypoxic stimulation;high dose bLF intervention group:daily bLF(7 g/L)+oral feeding with LPS gavage+hypoxic stimulation;low dose bLF intervention group:daily bLF(2 g/L)+oral feeding with LPS gavage+hypoxic stimulation.Histopathological analysis was performed by HE staining.The expression levels of interleukin-1β (IL-1β)and interleukin-6(IL-6)in intestinal mucosa were detected by enzyme linked immunosorbent assay(ELISA).Results(1)Morphological observation:the intestinal wall of model group was thin,and there were different degrees of pneumoconiosis and effusion in intestinal cavity.Under the microscopy,it could be observed that the intestinal tissue necrosis was serious,the intestinal villi fell off,glands arranged disorderly,epithelial edema was significant,the lamina propria and submucosa had severely edema and were separated,and there were a large number of inflammatory cells infiltrated.The above-mentioned manifestations were alleviated in the high-dose and low-dose bLF intervention groups,and no significant abnormalities were found in the control group.(2)The expression of IL-1β and IL-6 in intestinal tissue:the tissue concentration of IL-1β and IL-6 in the model group rats[(380.89±20.25)ng/L,(485.12±31.44)ng/L]were significantly higher than those in the control group[(270.69±45.58)ng/L,(212.62±89.46)ng/L](q=9.785,14.030,all P<0.01).The expression of IL-1βand IL-6 in mucosal tissue of ileum was significantly inhibited in hypoxic and LPS-stimulated rats fed with bLF(IL-1β:q=9.105,8.761,all P<0.01;IL-6:q=8.175,8.996,all P<0.01).Th

关 键 词：牛乳铁蛋白 坏死性小肠结肠炎 白细胞介素-1Β 白细胞介素-6 

分 类 号：R722[医药卫生—儿科]