柠檬苦素对溃疡性结肠炎大鼠肠道损伤和肠道菌群紊乱的改善作用及机制

张霞; 贾慧宇; 康金旺; 赵汉清

doi:10.6039/j.issn.1001-0408.2024.01.09

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柠檬苦素对溃疡性结肠炎大鼠肠道损伤和肠道菌群紊乱的改善作用及机制

药学研究 | 更新时间：2024-01-11

- 柠檬苦素对溃疡性结肠炎大鼠肠道损伤和肠道菌群紊乱的改善作用及机制
- Improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis and its mechanism
- 中国药房 2024年35卷第1期页码：51-56
- 作者机构：
  
  1.河北北方学院附属第二医院消化内科，河北张家口　075100
  2.河北北方学院附属第二医院检验科，河北张家口　075100
  3.河北北方学院附属第二医院中医科，河北张家口　075100
- 作者简介：
  
  副主任医师。研究方向：溃疡性结肠炎。E-mail：zhangxiaxia5287@163.com
- 基金信息：
  
  河北省医学科学研究课题计划项目(20210853)
- DOI：10.6039/j.issn.1001-0408.2024.01.09
  中图分类号： R965
- 纸质出版日期：2024-01-15，
  
  收稿日期：2023-08-07，
  
  修回日期：2023-11-27，
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张霞,贾慧宇,康金旺等.柠檬苦素对溃疡性结肠炎大鼠肠道损伤和肠道菌群紊乱的改善作用及机制 ^Δ[J].中国药房,2024,35(01):51-56.

ZHANG Xia,JIA Huiyu,KANG Jinwang,et al.Improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis and its mechanism[J].ZHONGGUO YAOFANG,2024,35(01):51-56.
张霞,贾慧宇,康金旺等.柠檬苦素对溃疡性结肠炎大鼠肠道损伤和肠道菌群紊乱的改善作用及机制 ^Δ[J].中国药房,2024,35(01):51-56. DOI： 10.6039/j.issn.1001-0408.2024.01.09.

ZHANG Xia,JIA Huiyu,KANG Jinwang,et al.Improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis and its mechanism[J].ZHONGGUO YAOFANG,2024,35(01):51-56. DOI： 10.6039/j.issn.1001-0408.2024.01.09.

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（

＜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（

＜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（

＜0.05），且具有剂量依赖性（

＜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（

＞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。

Abstract

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 （

＜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 （

＜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 （

＜0.05）， and in a dose-dependent manner （

＜0.05）； there was no significant difference in various indexes between sulfasalazine group and limonin high-dose group （

＞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.

关键词

柠檬苦素溃疡性结肠炎肠道损伤肠道菌群高迁移率族蛋白B1/晚期糖基化终末产物受体信号通路

Keywords

ulcerative colitisintestinal injuryintestinal floraHMGB1/RAGE signaling pathway

references

BUIE M J，QUAN J，WINDSOR J W，et al. Global hospitalization trends for Crohn’s disease and ulcerative colitis in the 21st century：a systematic review with temporal analyses[J]. Clin Gastroenterol Hepatol，2023，21（9）：2211-2221.

吴澎泞，熊帅，杨婉卿，等. 托法替尼治疗溃疡性结肠炎的研究进展[J]. 中国药房，2022，33（18）：2299-2304.

WU P N，XIONG S，YANG W Q，et al. Research advances of tofacitinib in the treatment of ulcerative colitis[J]. China Pharm，2022，33（18）：2299-2304.

WANG R，CHEN T，WANG Q，et al. Total flavone of Abelmoschus manihot ameliorates stress-induced microbial alterations drive intestinal barrier injury in DSS colitis[J]. Drug Des Devel Ther，2021，15：2999-3016.

SONG C Q，CHEN J X，LI X T，et al. Limonin ameliorates dextran sulfate sodium-induced chronic colitis in mice by inhibiting PERK-ATF4-CHOP pathway of ER stress and NF-κB signaling[J]. Int Immunopharmacol，2021，90：107161.

ARAB H H，AL-SHORBAGY M Y，SAAD M A. Activation of autophagy and suppression of apoptosis by dapagliflozin attenuates experimental inflammatory bowel disease in rats：targeting AMPK/mTOR，HMGB1/RAGE and Nrf2/HO-1 pathways[J]. Chem Biol Interact，2021，335：109368.

杜鹏程，韩璠，谷九莲. 溃疡性结肠炎患者血清单核细胞趋化蛋白-1、高迁移率族蛋白B1、肿瘤坏死因子-α、白细胞介素-6和白细胞介素-10水平与肠道菌群的相关性[J]. 新乡医学院学报，2021，38（4）：370-373.

DU P C，HAN F，GU J L. Correlation between serum monocyte chemoattractant protein-1，high mobility group protein B1，tumor necrosis factor-α，interleukin-6，interleukin-10 levels and intestinal flora in patients with ulcerative colitis[J]. J Xinxiang Med Univ，2021，38（4）：370-373.

王钰嘉，于千惠，卢雨微，等. 穴位埋线联合艾灸对溃疡性结肠炎大鼠结肠组织IL-6/JAK/STAT3信号通路的影响[J]. 针刺研究，2022，47（6）：525-530.

WANG Y J，YU Q H，LU Y W，et al. Effect of moxibustion combined with acupoint catgut embedding on IL-6/JAK/STAT3 signaling pathway in colonic mucosa of ulcerative colitis rats[J]. Acupunct Res，2022，47（6）：525-530.

黄爽，陈琛，黄波. 柠檬苦素对营养性肥胖大鼠脂质代谢和肠道菌群的影响[J]. 吉林大学学报（医学版），2022，48（4）：858-865.

HUANG S，CHEN C，HUANG B. Effects of limonin on lipid metabolism and intestinal flora in nutritionally obese rats[J]. J Jilin Univ Med Ed，2022，48（4）：858-865.

陈泰宇，唐学贵，蒋小东，等. 基于Nrf2/ARE信号通路探讨硫氢化钠对溃疡性结肠炎大鼠肠黏膜损伤的影响[J]. 中国现代医学杂志，2022，32（19）：38-43.

CHEN T Y，TANG X G，JIANG X D，et al. Effects of NaHS on intestinal mucosal injury in ulcerative colitis rats based on Nrf2/ARE signaling pathway[J]. China J Mod Med，2022，32（19）：38-43.

钟焕英，刘礼剑，卫家润，等. 中药对微小RNA调控溃疡性结肠炎相关信号通路的干预作用研究进展[J]. 中国药房，2023，34（17）：2167-2171.

ZHONG H Y，LIU L J，WEI J R，et al. Research progress on the intervention effects of Chinese medicine on microRNA regulating the signaling pathway of ulcerative colitis[J]. China Pharm，2023，34（17）：2167-2171.

LI Y Y，WANG X J，SU Y L，et al. Baicalein ameliorates ulcerative colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s[J]. Acta Pharmacol Sin，2022，43（6）：1495-1507.

GU M，SUN J，QI C，et al. The gastrointestinal fate of limonin and its effect on gut microbiota in mice[J]. Food Funct，2019，10（9）：5521-5530.

LIU S J，ZHANG S F，LV X Y，et al. Limonin ameliorates ulcerative colitis by regulating STAT3/miR-214 signaling pathway[J]. Int Immunopharmacol，2019，75：105768.

吴子俊，聂湘江，方文悠，等. 葛根芩连结肠定位胶囊对溃疡性结肠炎大鼠疾病活动指数和结肠黏膜损伤指数的影响[J]. 安徽中医药大学学报，2021，40（5）：74-78.

WU Z J，NIE X J，FANG W Y，et al. Effect of Gegen qinlian colon-specific capsule on disease activity index and colonic mucosal damage index in rats with ulcerative colitis[J]. J Anhui Univ Chin Med，2021，40（5）：74-78.

朱锐，何灵，唐瑶，等. 奥曲肽治疗TNBS致大鼠溃疡性结肠炎及其机制研究[J]. 中国药理学通报，2020，36（9）：1276-1281.

ZHU R，HE L，TANG Y，et al. Treatment of ulcerative colitis induced by TNBS with octreotide in rats and its mechanism[J]. Chin Pharmacol Bull，2020，36（9）：1276-1281.

CHEN L，LI L，HAN Y，et al. Tong-fu-li-Fei decoction exerts a protective effect on intestinal barrier of sepsis in rats through upregulating ZO-1/occludin/claudin-1 expression[J]. J Pharmacol Sci，2020，143（2）：89-96.

LEE J W，COWLEY E S，WOLF P G，et al. Formation of secondary allo-bile acids by novel enzymes from gut Firmicutes[J]. Gut Microbes，2022，14（1）：2132903.

ZHANG W Y，ZOU G L，LI B，et al. Fecal microbiota transplantation （FMT） alleviates experimental colitis in mice by gut microbiota regulation[J]. J Microbiol Biotechnol，2020，30（8）：1132-1141.

吴军城，赵立国，张立文. 迷迭香酸调节HMGB1/RAGE信号轴对溃疡性结肠炎大鼠肠屏障损伤及肠道菌群失调的影响[J]. 中国病原生物学杂志，2023，18（11）：1257-1263.

WU J C，ZHAO L G，ZHANG L W. Effect of rosmarinic acid on intestinal barrier damage and gut microbiota imbalance in rats with ulcerative colitis by regulating the HMGB1/RAGE signal axis[J]. J Pathog Biol，2023，18（11）：1257-1263.

ARAB H H，EID A H，MAHMOUD A M，et al. Linag- liptin mitigates experimental inflammatory bowel disease in rats by targeting inflammatory and redox signaling[J]. Life Sci，2021，273：119295.

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