摘要
目的探究柠檬苦素对溃疡性结肠炎(UC)大鼠肠道损伤和肠道菌群紊乱的改善作用及机制。方法构建UC大鼠模型,将建模成功的70只大鼠随机分为模型组和柠檬苦素低、中、高剂量组(12.5、25、50 mg/kg)以及柳氮磺胺吡啶组(阳性对照组,500 mg/kg),每组14只;另取14只大鼠作为对照组。各组大鼠灌胃相应药液或等量生理盐水,每天1次,连续2周。末次给药结束24 h后,观察大鼠一般情况并称重,取结肠组织进行结肠黏膜损伤指数(CMDI)评分;检测大鼠结肠组织中白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)水平;观察大鼠结肠组织病理学变化;检测大鼠结肠组织中紧密连接蛋白1(Claudin-1)、闭合蛋白(Occludin)、闭锁小带蛋白1(ZO-1)、高迁移率族蛋白B1(HMGB1)、晚期糖基化终末产物受体(RAGE)蛋白的表达水平;基于16S rRNA检测大鼠肠道菌群的相对丰度。结果与对照组相比,模型组大鼠精神状态不佳、皮毛较暗、情绪烦躁易发怒,结肠组织腺体排列杂乱,出现炎症细胞浸润和细胞坏死、水肿现象;CMDI评分和结肠组织中IL-1β、IL-6、TNF-α水平,HMGB1、RAGE蛋白表达水平以及肠道变形菌门、拟杆菌门菌群的相对丰度均显著升高(P<0.05);体重和结肠组织中Claudin-1、Occludin、ZO-1蛋白表达水平以及肠道厚壁菌门菌群的相对丰度均显著降低(P<0.05)。与模型组相比,柠檬苦素各剂量组大鼠一般情况和结肠组织病理损伤均改善,上述指标水平均显著逆转(P<0.05),且具有剂量依赖性(P<0.05);柳氮磺胺吡啶组与柠檬苦素高剂量组大鼠各项指标比较,差异均无统计学意义(P>0.05)。结论柠檬苦素可改善UC模型大鼠肠道损伤及肠道菌群紊乱,其作用机制可能与下调HMGB1/RAGE信号通路活性有关。
OBJECTIVE To investigate the improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis(UC)and its mechanism.METHODS UC rat models were established,and 70 rats with successful modeling were randomly divided into model group,limonin low-,medium-,and high-dose groups(12.5,25,50 mg/kg),and sulfasalazine group(positive control group,500 mg/kg),with 14 rats in each group.Another 14 rats were selected as the control group.After modeling,each group was given the corresponding drug or equal amount of normal saline,once a day,for 2 weeks.Twenty-four hours after the last administration,the general condition of rats was observed and the body weight was measured,and colon tissue was collected for colonic mucosal damage index(CMDI)scoring;the levels of interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)in colon tissue were detected;the pathological changes of colon tissue were observed;the protein expressions of Claudin-1,Occludin,ZO-1,high mobility group protein B1(HMGB1)and receptor for advanced glycation end products(RAGE)in colon tissue were detected;fecal 16S rRNA sequencing was used to detect the relative abundance of intestinal microbiota in rats.RESULTS Compared with the control group,the rats in the model group were in poor mental state,with darker fur,irritable mood,disordered arrangement of colon glands,inflammatory cell infiltration,cell necrosis and edema;CMDI score,the levels of IL-1β,IL-6 and TNF-α,protein expressions of HMGB1 and RAGE in colon tissue,the relative abundance of Proteobacteria and Bacteroidetes were significantly increased(P<0.05);body weight,the protein expressions of Claudin-1,Occludin and ZO-1 in colon tissue,the relative abundance of Firmicutes in the intestine were significantly decreased(P<0.05).Compared with the model group,general situation and pathological damage of colonic tissue in limonin groups were improved,the levels of the above indicators were significantly reversed(P<0.05),and in a dose-dependent manner(P<0.05);there was no significant difference in various indexes between sulfasalazine group and limonin high-dose group(P>0.05).CONCLUSIONS Limonin can improve intestinal injury and intestinal flora disturbance in UC model rats,the mechanism of which may be associated with the down-regulation of HMGB1/RAGE signaling pathway.
作者
张霞
贾慧宇
康金旺
赵汉清
ZHANG Xia;JIA Huiyu;KANG Jinwang;ZHAO Hanqing(Dept.of Gastroenterology,the Second Affiliated Hospital of Hebei North University,Hebei Zhangjiakou 075100,China;Dept.of Clinical Laboratory,the Second Affiliated Hospital of Hebei North University,Hebei Zhangjiakou 075100,China;Dept.of Traditional Chinese Medicine,the Second Affiliated Hospital of Hebei North University,Hebei Zhangjiakou 075100,China)
出处
《中国药房》
CAS
北大核心
2024年第1期51-56,共6页
China Pharmacy
基金
河北省医学科学研究课题计划项目(No.20210853)。
