基于LncRNA ELFN1-AS1表达探究BrMC对溃疡性结肠炎相关结直肠癌变的调控作用  

The regulatory effect of BrMC on colorectal cancer associated with ulcerative colitis based on LncRNA ELFN1-AS1 expression

作　　者：张荣菊 苗玉[1] 周玮玮[1] 田亮 ZHANG Rongju;MIAO Yu;ZHOU Weiwei;TIAN Liang(Department of Pathology,Cangzhou Central Hospital,Cangzhou 061600,Hebei,China)

机构地区：[1]沧州市中心医院病理科,河北沧州061600

出　　处：《西部医学》2025年第4期490-496,504,共8页Medical Journal of West China

基　　金：河北省医学科学研究课题计划(20240590)。

摘　　要：目的观察8-溴-7-甲氧基白杨素(BrMC)对溃疡性结肠炎相关结直肠癌变(UCAC)小鼠的疗效,并基于长链非编码RNA(LncRNA)ELFN1-AS1表达探讨BrMC调控小鼠UCAC的分子机制。方法采用葡聚糖硫酸钠(DSS)联合氧化偶氮甲烷(AOM)法构建小鼠UCAC模型,将15只SPF级C57BL/6小鼠随机分为对照组、模型组、BrMC组,每组5只。实时荧光定量聚合酶链式反应(qRT-PCR)检测3组小鼠结肠组织ELFN1-AS1表达变化。另选取50只SPF级C58BL/6小鼠分为对照组、模型组、BrMC组、BrMC+NC组、BrMC+ELFN1-AS1组,每组10只,除对照组外的其余4组小鼠均构建UCAC模型,给予BrMC灌胃或尾静脉注射ELFN1-AS1阴性对照(NC)、过表达ELFN1-AS1质粒脂质体复合物;给药结束后,观察各组小鼠一般情况,测定各组小鼠的体质量与疾病活动指数(DAI),检查各组小鼠结肠病理学损伤及成瘤情况,苏木精-伊红(HE)染色观察各组小鼠结肠组织病理学变化,末端脱氧核苷酸转移酶介导的dUTP原位末端标记(TUNEL)染色检测各组小鼠结肠组织细胞凋亡情况,酶联免疫吸附法(ELISA)检测各组小鼠结肠组织TNF-α、IL-1β、IL-6、IL-12水平,qRT-PCR检测各组结肠组织中ELFN1-AS1表达水平。结果模型组小鼠结肠组织内ELFN1-AS1相对表达量较对照组显著上调(P<0.05),BrMC组小鼠结肠组织内ELFN1-AS1相对表达量较模型组显著下调(P<0.05)。进一步研究表明,与模型组比较,BrMC组小鼠活动程度、精神状态等均得到明显改善,体质量显著升高(P<0.05),DAI评分显著降低(P<0.05),结肠黏膜充血、水肿及溃烂等现象明显减轻,肿瘤数目显著减少(P<0.05),结肠黏膜组织上皮细胞损伤、炎症细胞浸润程度均减小,TUNEL标记的凋亡细胞数目比例显著降低(P<0.05),结肠组织TNF-α、IL-1β、IL-6、IL-12水平显著下降(P<0.05),同时,结肠组织内ELFN1-AS1相对表达量显著下调(P<0.05)。与BrMC组比较,BrMC+ELFN1-AS1组小鼠活动程度下降、精神萎靡,体质量Objective To observe the curative effect of 8-bromo-7-methoxychrysin(BrMC)on ulcerative colitis associated colorectal cancer(UCAC)mice,and explore the molecular mechanism of BrMC regulation of UCAC mice based on the expression of long non-coding RNA(LncRNA)ELFN1-AS1.Methods The UCAC model of C57BL/6 mice was established by sodium glucan sulfate(DSS)combined with azomethane oxide(AOM),the mice were given BrMC intragastric treatment,and the expression of ELNF1-AS1 in colon tissue was detected by real-time quantitative fluorescence polymerase chain reaction(qRT-PCR).The experiment was divided into 5 groups,including control group,model group,BrMC group,BrMC+NC group,and BrMC+ELFN1-AS1 group,with 10 mice in each group.UCAC model was constructed for the other 4 groups except the control group,BrMC was given intragastric administration or caudal vein injection of ELNF1-AS1 negative control(NC)and overexpressed ELFN1-AS1 plasmid liposome complex.After the administration,the general conditions of mice in each group were observed,body mass and disease activity index(DAI)of mice in each group were determined,pathological injury and tumorigenesis of colon of mice in each group were examined,hematoxylin-eosin(HE)staining was performed to observe the histopathological changes of colon,terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL)was used to detect the apoptosis of colon tissue cells in each group,enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of inflammatory cytokines tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6 and IL-12 in colon tissue of mice in each group,and the expression levels of ELFN1-AS1 in colon tissue of mice in each group were detected by qRT-PCR.Results The relative expression level of ELFN1-AS1 in colon tissue of mice in model group was significantly up-regulated compared with that in control group(P<0.05),and the relative expression level of ELFN1-AS1 in colon tissue of mice in BrMC group was significantly down-regulated compared with t

关 键 词：溃疡性结肠炎相关结直肠癌变 小鼠 8-溴-7-甲氧基白杨素 LncRNA ELFN1-AS1 

分 类 号：R574.62[医药卫生—消化系统]