LR12肽通过调控TLR-4/NF-κB信号通路对坏死性小肠结肠炎新生小鼠肠道损伤的影响  

Effect of LR12 peptide on intestinal injury in neonatal mice with necrotic enterocolitis by regulating TLR-4/NF-κB signaling pathways

作　　者：占彩霞[1] 廖镇宇[1] 黄瑞文[1] 刘银芝[1] 杨慧[1] ZHAN Caixia;LIAO Zhenyu;HUANG Ruiwen;LIU Yinzhi;YANG Hui(Department of Neonatology,Hunan Children’s Hospital,Hunan Province,Changsha 410007,China)

机构地区：[1]湖南省儿童医院新生儿科,湖南长沙410007

出　　处：《中国医药导报》2022年第1期9-12,22,共5页China Medical Herald

基　　金：湖南省卫生计生委科研计划课题项目(B20180477)。

摘　　要：目的探讨LR12肽对坏死性小肠结肠炎(NEC)新生小鼠肠道损伤的影响及其作用机制。方法SPF级C57BL/6小鼠18只(雌性6只,雄性12只),8周龄,体重16~23 g。雌鼠受孕后产幼鼠60只,根据随机数字表法分为对照组、模型组、LR12-scr组和LR12组,每组15只。对照组不采取任何操作,其余三组建立NEC模型。模型构建成功后,LR12-scr组腹腔注射5 mg/kg LR12 scramble,LR12组腹腔注射5 mg/kg LR12肽,对照组和模型组腹腔注射等剂量的溶剂,1次/d,连续3 d。比较各组幼鼠的各项指标。结果与对照组比较,模型组临床症状积分,肠组织病理评分,肠黏膜通透性,肿瘤坏死因子-α(TNF-α)、白介素(IL)-1β和IL-6水平及髓细胞触发受体1、TLR-4、MyD88、NF-κB p65等蛋白表达水平升高,体重及IκBα蛋白表达水平降低,差异均有统计学意义(P<0.05)。与模型组比较,LR12组临床症状积分,肠组织病理评分,肠黏膜通透性,TNF-α、IL-1β和IL-6水平及TREM1、TLR-4、MyD88、NF-κB p65等蛋白表达水平降低,体重及IκBα蛋白表达水平升高,差异均有统计学意义(P<0.05)。LR12-scr组以上各指标与模型组比较,差异均无统计学意义(P>0.05)。结论LR12肽可改善NEC新生小鼠肠黏膜通透性,降低肠组织炎症反应,减轻肠道损伤,其机制可能与抑制TLR-4/NF-κB信号通路活化有关。Objective To investigate the mechanism of LR12 peptide on intestinal damage in necrotic enterocolitis(NEC)in neonatal mice.Methods A total of 18 SPF C57 BL/6 mice(6 females,12 males),8 weeks,weight 16-23 g.Sixty pups born after the female rat pregnancy,they were divided into control group,model group,LR12-scr group and LR12 group according to random number table method,with 15 pups in each group.The control group did not take any operation,and the other three groups established NEC model.After successful model construction,lR12-scr group was intraperitoneally injected with 5 mg/kg LR12 scramble,LR12 group was intraperitoneally injected with 5 mg/kg LR12 peptide,control group and model group were intraperitoneally injected with equal dose of solvent once a day for consecutive three days.The indexes of young rats in each group were compared.Results Compared with the control group,clinical symptom score,intestinal histopathological score,the intestinal permeability,the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1βand IL-6 and the protein expressions levels of triggering receptor expressed on myeloid cells-1,TLR-4,MyD88,and NF-κB p65 were increased in the model group,while weight and the expression levels of IκBαwere dereased,the differences were statistically significant(P<0.05).Compared with the model group,clinical symptom score,intestinal histopathological score,the intestinal permeability,the levels of TNF-α,IL-1β,and IL-6 and the protein expression levels of TREM1,TLR-4,MyD88,and NF-κB p65 were decreased in the LR12 group,while weight and the expression level of IκBαwere increased,the differences were statistically significant(P<0.05).There were no statistical signficances in the above indicators between LR12-scr group and model group(P>0.05).Conclusion LR12 peptide has improved intestinal permeability,reduced intestinal inflammation and injury in NEC neonatal mice,and the mechanism may be related to inhibiting TLR-4/NF-κB signaling pathway activation.

关 键 词：LR12肽 TLR-4/NF-κB信号通路 坏死性小肠结肠炎 炎症 

分 类 号：R33[医药卫生—人体生理学]