溃羊灵灌肠剂通过降低肠道NETs水平和促进HuR/VDR信号通路改善溃疡性结肠炎小鼠。

IF 4.2 2区 医学 Q2 IMMUNOLOGY
Journal of Inflammation Research Pub Date : 2025-01-08 eCollection Date: 2025-01-01 DOI:10.2147/JIR.S492818
Dong Zhang, Zeming Zhu, Zhangyou He, Siwei Duan, Qincheng Yi, Min Qiu, Xingzhen Dai, Guang Su, Kexin Li, Lin Xu, Donghou Liu, Yabin Wu, Yong Gao, Ruliu Li, Shaoju Guo
{"title":"溃羊灵灌肠剂通过降低肠道NETs水平和促进HuR/VDR信号通路改善溃疡性结肠炎小鼠。","authors":"Dong Zhang, Zeming Zhu, Zhangyou He, Siwei Duan, Qincheng Yi, Min Qiu, Xingzhen Dai, Guang Su, Kexin Li, Lin Xu, Donghou Liu, Yabin Wu, Yong Gao, Ruliu Li, Shaoju Guo","doi":"10.2147/JIR.S492818","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Kuiyangling is a traditional Chinese medicine formula used for the treatment of ulcerative colitis, but the specific mechanism remains unclear. Imbalance in NETs regulation is one of the important factors contributing to the onset of ulcerative colitis (UC). The HuR/VDR signaling pathway plays a significant role in restoring the intestinal mucosal barrier in UC. The aim of this study is to explore the mechanism of Kuiyangling in the treatment of ulcerative colitis.</p><p><strong>Methods: </strong>A mouse model of ulcerative colitis using 3% DSS water was considered, and model, normal, Kuiyangling medium- (5 g·kg<sup>-1</sup>) and high-dose (10 g·kg<sup>-1</sup>), and mesalazine (50 mg·kg<sup>-1</sup>) groups were created. Measurements of colon length, spleen index, histopathological variances, subcellular structure observations, ROS content, and NET-related proteins (PAD4, MPO, citH3) were obtained through HE staining, electron microscopy, live imaging, and Western blotting assays. Immunohistochemistry and immunofluorescence analyses were conducted to assess the levels of HuR/VDR protein complex, ZO-1, Occludin, Claudin-7, and intestinal NETs. An ELISA kit was utilized to determine cytokine levels, LC-MS was performed to analyze the composition of Kuiyangling, and next-generation sequencing was conducted for detection of the intestinal mucosal transcriptome.</p><p><strong>Results: </strong>Kuiyangling reduced DAI, splenic index, and ROS content; maintained mucosal structure; decreased inflammation; and increased colon length and body mass index. Western blotting indicated that Kuiyangling reduced PAD4,MPO, and citH3 levels. Kuiyangling decreased NETs and increased the expression levels of ZO-1, Occludin, and Claudin-7, as well as up-regulating HuR, VDR, and HuR/VDR proteins. Kuiyangling reduced IL-1β, IL-6, and TNF-α levels while increasing TGF-β, IL-10, and IL-37 levels. Kuiyangling reduced inflammatory response proteins and elevated the levels of anti-inflammatory and intestinal barrier proteins, possibly inhibiting the TNF and oxidative phosphorylation signaling pathways.</p><p><strong>Conclusion: </strong>Kuiyangling enema in treating ulcerative colitis in mice, associated with a reduction in intestinal NETs and enhancement of HuR-mediated intestinal barrier signaling pathways.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"381-403"},"PeriodicalIF":4.2000,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725280/pdf/","citationCount":"0","resultStr":"{\"title\":\"Kuiyangling Enema Alleviates Ulcerative Colitis Mice by Reducing Levels of Intestinal NETs and Promoting HuR/VDR Signaling.\",\"authors\":\"Dong Zhang, Zeming Zhu, Zhangyou He, Siwei Duan, Qincheng Yi, Min Qiu, Xingzhen Dai, Guang Su, Kexin Li, Lin Xu, Donghou Liu, Yabin Wu, Yong Gao, Ruliu Li, Shaoju Guo\",\"doi\":\"10.2147/JIR.S492818\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Kuiyangling is a traditional Chinese medicine formula used for the treatment of ulcerative colitis, but the specific mechanism remains unclear. Imbalance in NETs regulation is one of the important factors contributing to the onset of ulcerative colitis (UC). The HuR/VDR signaling pathway plays a significant role in restoring the intestinal mucosal barrier in UC. The aim of this study is to explore the mechanism of Kuiyangling in the treatment of ulcerative colitis.</p><p><strong>Methods: </strong>A mouse model of ulcerative colitis using 3% DSS water was considered, and model, normal, Kuiyangling medium- (5 g·kg<sup>-1</sup>) and high-dose (10 g·kg<sup>-1</sup>), and mesalazine (50 mg·kg<sup>-1</sup>) groups were created. Measurements of colon length, spleen index, histopathological variances, subcellular structure observations, ROS content, and NET-related proteins (PAD4, MPO, citH3) were obtained through HE staining, electron microscopy, live imaging, and Western blotting assays. Immunohistochemistry and immunofluorescence analyses were conducted to assess the levels of HuR/VDR protein complex, ZO-1, Occludin, Claudin-7, and intestinal NETs. An ELISA kit was utilized to determine cytokine levels, LC-MS was performed to analyze the composition of Kuiyangling, and next-generation sequencing was conducted for detection of the intestinal mucosal transcriptome.</p><p><strong>Results: </strong>Kuiyangling reduced DAI, splenic index, and ROS content; maintained mucosal structure; decreased inflammation; and increased colon length and body mass index. Western blotting indicated that Kuiyangling reduced PAD4,MPO, and citH3 levels. Kuiyangling decreased NETs and increased the expression levels of ZO-1, Occludin, and Claudin-7, as well as up-regulating HuR, VDR, and HuR/VDR proteins. Kuiyangling reduced IL-1β, IL-6, and TNF-α levels while increasing TGF-β, IL-10, and IL-37 levels. Kuiyangling reduced inflammatory response proteins and elevated the levels of anti-inflammatory and intestinal barrier proteins, possibly inhibiting the TNF and oxidative phosphorylation signaling pathways.</p><p><strong>Conclusion: </strong>Kuiyangling enema in treating ulcerative colitis in mice, associated with a reduction in intestinal NETs and enhancement of HuR-mediated intestinal barrier signaling pathways.</p>\",\"PeriodicalId\":16107,\"journal\":{\"name\":\"Journal of Inflammation Research\",\"volume\":\"18 \",\"pages\":\"381-403\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2025-01-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725280/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Inflammation Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/JIR.S492818\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inflammation Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/JIR.S492818","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

目的:苦养灵是治疗溃疡性结肠炎的中药方剂,但其具体作用机制尚不清楚。神经网络调节失衡是导致溃疡性结肠炎(UC)发病的重要因素之一。HuR/VDR信号通路在UC的肠黏膜屏障恢复中起重要作用。本研究旨在探讨溃羊灵治疗溃疡性结肠炎的作用机制。方法:建立3% DSS水致溃疡性结肠炎小鼠模型,分为模型组、正常组、溃羊灵中(5 g·kg-1)、高剂量组(10 g·kg-1)、美萨拉嗪组(50 mg·kg-1)。通过HE染色、电镜、活体成像和Western blotting测定结肠长度、脾脏指数、组织病理学差异、亚细胞结构观察、ROS含量和net相关蛋白(PAD4、MPO、citH3)。通过免疫组织化学和免疫荧光分析评估HuR/VDR蛋白复合物、ZO-1、Occludin、Claudin-7和肠道NETs的水平。采用ELISA试剂盒检测细胞因子水平,LC-MS分析苦羊灵成分,下一代测序检测肠黏膜转录组。结果:苦养灵降低DAI、脾指数及ROS含量;维持粘膜结构;减少炎症;增加了结肠长度和体重指数。Western blotting结果显示,苦杨凌降低了PAD4、MPO和citH3水平。苦养灵降低NETs,上调ZO-1、Occludin、Claudin-7蛋白表达,上调HuR、VDR、HuR/VDR蛋白表达。苦养灵降低IL-1β、IL-6、TNF-α水平,升高TGF-β、IL-10、IL-37水平。苦杨灵降低炎症反应蛋白,提高抗炎蛋白和肠道屏障蛋白水平,可能抑制TNF和氧化磷酸化信号通路。结论:苦养灵灌肠治疗小鼠溃疡性结肠炎,与肠道NETs减少和hur介导的肠道屏障信号通路增强有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Kuiyangling Enema Alleviates Ulcerative Colitis Mice by Reducing Levels of Intestinal NETs and Promoting HuR/VDR Signaling.

Purpose: Kuiyangling is a traditional Chinese medicine formula used for the treatment of ulcerative colitis, but the specific mechanism remains unclear. Imbalance in NETs regulation is one of the important factors contributing to the onset of ulcerative colitis (UC). The HuR/VDR signaling pathway plays a significant role in restoring the intestinal mucosal barrier in UC. The aim of this study is to explore the mechanism of Kuiyangling in the treatment of ulcerative colitis.

Methods: A mouse model of ulcerative colitis using 3% DSS water was considered, and model, normal, Kuiyangling medium- (5 g·kg-1) and high-dose (10 g·kg-1), and mesalazine (50 mg·kg-1) groups were created. Measurements of colon length, spleen index, histopathological variances, subcellular structure observations, ROS content, and NET-related proteins (PAD4, MPO, citH3) were obtained through HE staining, electron microscopy, live imaging, and Western blotting assays. Immunohistochemistry and immunofluorescence analyses were conducted to assess the levels of HuR/VDR protein complex, ZO-1, Occludin, Claudin-7, and intestinal NETs. An ELISA kit was utilized to determine cytokine levels, LC-MS was performed to analyze the composition of Kuiyangling, and next-generation sequencing was conducted for detection of the intestinal mucosal transcriptome.

Results: Kuiyangling reduced DAI, splenic index, and ROS content; maintained mucosal structure; decreased inflammation; and increased colon length and body mass index. Western blotting indicated that Kuiyangling reduced PAD4,MPO, and citH3 levels. Kuiyangling decreased NETs and increased the expression levels of ZO-1, Occludin, and Claudin-7, as well as up-regulating HuR, VDR, and HuR/VDR proteins. Kuiyangling reduced IL-1β, IL-6, and TNF-α levels while increasing TGF-β, IL-10, and IL-37 levels. Kuiyangling reduced inflammatory response proteins and elevated the levels of anti-inflammatory and intestinal barrier proteins, possibly inhibiting the TNF and oxidative phosphorylation signaling pathways.

Conclusion: Kuiyangling enema in treating ulcerative colitis in mice, associated with a reduction in intestinal NETs and enhancement of HuR-mediated intestinal barrier signaling pathways.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Inflammation Research
Journal of Inflammation Research Immunology and Microbiology-Immunology
CiteScore
6.10
自引率
2.20%
发文量
658
审稿时长
16 weeks
期刊介绍: An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings on the molecular basis, cell biology and pharmacology of inflammation.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信