基于Th17/Treg免疫平衡研究黄芩醇提物治疗溃疡性结肠炎的作用机制

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中文摘要：目的:探究黄芩醇提物调节免疫平衡治疗溃疡性结肠炎(ulcerative colitis，UC)的作用及机制。方法:将24 只C57BL/6 小鼠随机分为正常组、模型组、美沙拉嗪组(500 mg·kg-1)、黄芩醇提物(400 mg·kg-1)组，每组6 只。采用2。5%葡聚糖硫酸钠(dextran sulfate sodium，DSS)的饮用水建立UC小鼠模型。每天观察各组小鼠体重及一般情况，d6 计算疾病活动指数(DAI);测量结肠长度;采用流式细胞术检测肠系膜淋巴结和脾脏中辅助性T细胞17(T helper 17，Th17)和调节性T细胞(regulatory T cells，Treg)比例;苏木精-伊红染色观察结肠组织损伤程度;酶联免疫吸附法检测结肠白细胞介素-6(interleukin，IL-6)，IL-10 和IL-1β的含量;蛋白免疫印迹法检测结肠Toll样受体4(Toll-like receptor 4，TLR4)、核因子κB p65(nuclear factor-kappa B，NF-κB p65)、p-NF-κB p65 及核因子κB抑制蛋白-α(I kappaB-alpha，IκB-α)的表达水平;气相色谱-质谱联用检测短链脂肪酸的含量;高内涵成像技术观察RAW264。7 细胞核转位情况。结果:黄芩醇提物可改善DSS诱导的小鼠结肠炎症状，恢复肠系膜淋巴结和脾脏中Th17/Treg免疫平衡，降低结肠组织中IL-1β和IL-6 水平、提高IL-10 表达水平，降低TLR4，NF-κB p65 和p-NF-κB p65 表达水平，提高IκB-α表达水平，提高肠道短链脂肪酸含量，抑制脂多糖诱导引起的核转位。结论:黄芩醇提物可以改善UC小鼠的症状，其机制可能是通过改善肠道稳态，抑制TLR4/NF-κB通路以恢复Th17/Treg免疫平衡。

外文标题：Exploration of mechanism of ethanol extract of Scutellaria baicalensis Georgi in treating ulcerative colitis based on Th17/Treg immune balance

外文摘要：Objective:To explore the effect and mechanism of alcohol extract of Scutellaria baicalensis Georgi on immune balance in treating ulcerative colitis(UC).Methods:24 C57BL/6 mice were randomly divided into control group,model group,mesalazine group,and Scutellaria baicalensis Georgi alcohol extract group(400 mg·kg-1,n =6 for each group).A mouse model of UC was established by drinking water containing 2.5%dextran sulfate sodium(DSS).The body weight and general condition of the mice in each group were observed every day,and the disease activity index(DAI)was calculated on the 6th day;the length of the colon was measured;the proportion of T helper 17(Th17)/regulatory T cells(Treg cells)in the mesenteric lymph nodes and spleen was detected by flow cytometry;hematoxylin-eosin staining was used to observe the degree of colon tissue damage;the levels of interleukin-6(IL-6),IL-10 and IL-1β in colon were detected by enzyme-linked immunosorbent assay;the expressions of Toll-like receptor 4(TLR4),nuclear factor-kappa B(NF-κB p65),p-NF-κB p65,and I kappaB-alpha(IκB-α)in colon were detected by Western blot;the main short chain fatty acids were detected by gas chromatography-mass spectrometry;high-content imaging was used to observe the nuclear translocation of RAW264.7 cells.Results:The alcohol extract of Scutellaria baicalensis Georgi improved the symptoms of colitis induced by DSS in mice,restored the Th17/Treg immune balance in mesenteric lymph nodes and spleen,reduced the levels of IL-1β and IL-6 in colon tissue,and increased the expression level of IL-10.It decreased the expressions of TLR4,NF-κB p65 and p-NF-κB p65,increased the expression of IκB-α,increased the content of intestinal short-chain fatty acids,and inhibited the nuclear translocation induced by LPS.Conclusion:The alcohol extract of Scutellaria baicalensis Georgi can improve the symptoms of UC mice,and the mechanism may be to restore Th17/Treg immune balance by improving intestinal homeostasis and inhibiting TLR4/NF-κB pathway.

外文关键词：

Scutellaria baicalensis Georgiethanol extractulcerative colitisTh17/Treg immune balanceTLR4/NF-κB signal pathwayshort-chain fatty acids

作者：

郭春雨、董红敬、郭兰萍、李佳、潘少斌、李庆军、王晓

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作者单位：

山东中医药大学药学院,济南 250300

齐鲁工业大学(山东省科学院)山东省分析测试中心山东省大型精密分析仪器应用技术重点实验室,济南 250014

中国中医科学院中药资源中心道地药材国家重点实验室培育基地,北京 100700

关键词：

黄芩醇提物溃疡性结肠炎 Th17/Treg免疫平衡 TLR4/NF-κB信号通路短链脂肪酸

基金：

山东省重点研发计划资助项目中央本级重大增减支项目齐鲁工业大学(山东省科学院)重大创新专项资助项目山东省医药卫生科技发展计划资助项目

项目编号：

2021CXGC01050820603022022JBZ02-042019WS554

出版年：

2024

中国新药杂志

中国医药科技出版社中国医药集团总公司中国药学会

中国新药杂志

CSTPCD北大核心

影响因子：1.039

ISSN：1003-3734

年,卷(期)：2024.33(4)

参考文献量38