[1]程迎迎,刘志琴,郑 凯,等.清肠化湿方调控Nrf2/ARE通路缓解溃疡性结肠炎的机制研究[J].南京师大学报(自然科学版),2024,(04):86-97.[doi:10.3969/j.issn.1001-4616.2024.04.010]
　Cheng Yingying,Liu Zhiqin,Zheng Kai,et al.Mechanistic Study of Qingchang Huashi Recipe Regulating the Nrf2/ARE Pathway to Alleviate Ulcerative Colitis[J].Journal of Nanjing Normal University(Natural Science Edition),2024,(04):86-97.[doi:10.3969/j.issn.1001-4616.2024.04.010]
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清肠化湿方调控Nrf2/ARE通路缓解溃疡性结肠炎的机制研究()
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《南京师大学报（自然科学版）》[ISSN:1001-4616/CN:32-1239/N]

卷:
期数:
2024年04期
页码:
86-97
栏目:
生物学
出版日期:
2024-12-15

文章信息/Info

Title:
Mechanistic Study of Qingchang Huashi Recipe Regulating the Nrf2/ARE Pathway to Alleviate Ulcerative Colitis
文章编号:
1001-4616(2024)04-0086-12
作者:
程迎迎1; 刘志琴2; 郑 凯3; 张 洁1; 徐 希2
(1.南京中医药大学附属医院,江苏省中医院检验科,江苏 南京 210029)
(2.南京理工大学分子代谢中心,江苏 南京 210094)
(3.南京中医药大学附属医院,江苏省中医院消化科,江苏 南京 210029)
Author(s):
Cheng Yingying1; Liu Zhiqin2; Zheng Kai3; Zhang Jie1; Xu Xi2
(1.Affiliated Hospital of Nanjing University of Chinese Medicine,Laboratory Department,Jiangsu Province Hospital of Chinese Medicine,Nanjing 210029,China)
(2.Center for Molecular Metabolism,Nanjing University of Science & Technology,Nanjing 210094,China)
(3.Affiliated Hospital of Nanjing University of Chinese Medicine,Department of Gastroenterology,Jiangsu Province Hospital of Chinese Medicine,Nanjing 210029,China)
关键词:
清肠化湿方; 溃疡性结肠炎; 氧化应激; 抗氧化反应元件
Keywords:
Qingchang Huashi Recipe(QHR); ulcerative colitis(UC); oxidative stress; antioxidant response element(ARE)
分类号:
R285.5
DOI:
10.3969/j.issn.1001-4616.2024.04.010
文献标志码:
A
摘要:
溃疡性结肠炎(ulcerative colitis,UC)是一类特发性的慢性炎症性肠道疾病,该病易反复,严重影响了患者的身体健康和生活质量. 本研究使用构建的小鼠溃疡性结肠炎模型,以氧化应激途径为重点,探讨清肠化湿方缓解UC的作用机制. 主要以DSS(Dextran Sodium Sulfate)作为诱导剂,构建小鼠溃疡性结肠炎模型. 每日测量小鼠体重,观察并记录小鼠粪便性状及出血情况. 实验结束后,留取小鼠结肠组织并记录结肠长度,分别从基因、蛋白和病理水平检测相关指标. 采用qRT-PCR检测结肠组织中HO-1、NQO-1、Keap1和Nrf2的表达; 核磁代谢组学分析各组结肠代谢物的变化并进行多元统计分析; 制备结肠病理切片并进行HE染色和免疫组化,HE染色后评估结肠病理炎症情况,免疫组化检测结肠组织中Keap1和Nrf2的表达. 结果显示,清肠化湿方(Qingchang Huashi Recipe,QHR)可提高溃疡性结肠炎小鼠的生存率; 与正常对照组(Ctrl)相比,DSS模型组小鼠体重降低,结肠长度变短(P<0.05),结肠组织病理炎症评分较高(P<0.05),抗氧化反应元件表达降低,差异均具有统计学意义(P<0.05); QHR给药后,与DSS组相比,小鼠体重升高,结肠长度变长(P<0.05),结肠组织病理炎症评分较低(P<0.05),结肠组织中HO-1、NHO-1、Nrf2表达升高,Keap1表达降低,差异均具有统计学意义(P<0.05). 本研究发现,QHR通过升高Nrf2从而上调ARE相关分子的表达,进而缓解过度氧化引起的肠道黏膜损伤.
Abstract:
Ulcerative colitis(UC)is a type of idiopathic chronic inflammatory bowel disease that tending to recur and significantly affecting the health and quality of life of patients. This study utilized a mouse model of UC,focusing on the oxidative stress pathway,to investigate the mechanisms through which Qingchang Huashi Recipe(QHR)alleviates UC. The primary methods involved inducing UC in mice using Dextran Sodium Sulfate(DSS). Daily measurements of mouse body weight,observation and recording of fecal characteristics and bleeding were conducted. After the treatment,the mouse colon length was measured,and colon tissue was collected. Various parameters were evaluated at the genetic,protein,and pathological levels. A portion of the collected colon tissue was subjected to qRT-PCR to assess the expression of HO-1,NQO-1,Keap1,and Nrf2 in colon tissue. Another portion was subjected to nuclear magnetic resonance metabolomics analysis to examine changes in colon metabolites among different groups and perform multivariate statistical analysis. A third portion was used to prepare colon pathological sections for hematoxylin and eosin(HE)staining and immunohistochemistry. HE staining was used to assess the pathological inflammation in colon tissue,and immunohistochemistry was employed to determine the expression of Keap1 and Nrf2 in colon tissue. The results demonstrated that QHR could increase the survival rate of mice with UC. Compared to the normal control group(Ctrl),mice in the DSS model group exhibited decreased body weight,shorter colon length(P<0.05),higher colon tissue pathological inflammation scores(P<0.05),and decreased expression of antioxidant response elements,all of which were statistically significant(P<0.05). After QHR administration,mice showed increased body weight,longer colon length(P<0.05),lower colon tissue pathological inflammation scores(P<0.05),and higher expression of HO-1,NHO-1,Nrf2,with a decrease in Keap1 expression,all of which were statistically significant(P<0.05)compared to the DSS group. This study found that QHR alleviated mucosal damage in the intestine caused by excessive oxidation by increasing Nrf2 expression and subsequently upregulating ARE-related molecules.

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备注/Memo

备注/Memo:
收稿日期:2023-10-29.
基金项目:国家中医临床研究基地开放课题(JD2019SZ07).
通讯作者:徐希,副教授,研究方向:感染性疾病的分子代谢. E-mail:xuxi@njust.edu.cn
更新日期/Last Update: 2024-12-15