首页|基于代谢组学研究中药固肠止泻丸治疗小鼠溃疡性结肠炎的机制

基于代谢组学研究中药固肠止泻丸治疗小鼠溃疡性结肠炎的机制

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目的:固肠止泻丸为溃疡性结肠炎患者的临床专家推荐用药.课题组前期研究发现固肠止泻丸对结肠炎的临床效果与肠道微生物密切相关,但固肠止泻丸在治疗溃疡性结肠炎方面的作用机制仍不明确.方法:采用2.5%葡聚糖硫酸钠建立溃疡性结肠炎小鼠模型,探讨固肠止泻丸对溃疡性结肠组织病理变化、疾病活动指数、炎症细胞因子的影响.同时采用液相色谱串联质谱技术检测小鼠血清样本中代谢物水平,并结合主成分分析和正交偏最小二乘法判别分析筛选出差异代谢物,采用MetaboAnalyst5.0确定与差异代谢物有关的代谢通路.结果:固肠止泻丸降低小鼠疾病活动指数评分,改善结肠组织形态,降低小鼠血清中的肿瘤坏死因子-α、白细胞介素-6、白细胞介素-lβ含量,升高白细胞介素4、白细胞介素-10含量.代谢组学结果显示,与固肠止泻丸调控相关的潜在差异代谢物共18个,主要涉及甘油磷脂代谢、不饱和脂肪酸的合成、亚麻酸代谢、α-亚麻酸代谢、嘌呤代谢.结论:固肠止泻丸对溃疡性结肠炎有一定的防治作用,其机制可能与调节甘油磷脂代谢、不饱和脂肪酸的合成、亚麻酸代谢、α-亚麻酸代谢、嘌呤代谢有关.
Metabolomics-based study on the mechanism of treatment of ulcerative colitis by the traditional Chinese medicine Guchang Zhixie Wan in mice
Objective:Guchang Zhixie Wan(GC)is recommended by clinical experts for the treatment of the patients with ulcerative colitis(UC).Previous studies of our group found that the clinical therapeutic effect of GC on colitis is closely related to intestinal microorganisms,but the mechanism of its action in the treatment of UC remains unclear.Methods:A mouse model of ulcerative colitis was established by using 2.5%dextran sulfate sodium to investigate the effects of Guchang Zhixie Wan on the histopathological changes of ulcerative colon,disease activity index,and inflammatory cytokines.Meanwhile,liquid chromatography-mass spectrometry was used to detect the levels of metabolites in the serum samples of mice.Combining principal components analysis and orthogonal partial least squares discrimination analysis,the differential metabolites were screened out.MetaboAnalyst 5.0 was used to determine the metabolic pathways related to the differential metabolites.Results:Guchang Zhixie Wan reduced the disease activity index score,improved the morphology of colon tissue,and decreased the serum levels of tumor necrosis factor-α,interleukin-6,and interleukin-1β,and increased the levels of interleukin-4 and interleukin-10 in serum of mice.The metabolomics results showed that a total of 19 potential differential metabolites associated with the regulatory effect of Guchang Zhixie Wan,mainly involving glycerophospholipid metabolism,unsaturated fatty acid synthesis,linolenic acid metabolism,α-linolenic acid metabolism,and purine metabolism.Conclusion:Guchang Zhixie Wan has a certain preventive effect on ulcerative colitis,and its mechanism may be related to the regulation of glycerophospholipid metabolism,unsaturated fatty acid synthesis,linolenic acid metabolism,α-linolenic acid metabolism,and purine metabolism.

Guchang Zhixie Wanulcerative colitisserum metabolomicsliquid chromatography-tandem mass spectrometry

范安琪、侯宝龙、朱洁、梁艳妮、王征

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陕西中药资源产业化省部共建协同创新中心/秦药特色资源研究开发国家重点实验室(培育)/陕西省创新药物研究中心/陕西中医药大学,咸阳 712083

固肠止泻丸 溃疡性结肠炎 代谢组学 液相色谱串联质谱

国家自然科学基金陕西省高等学校青年科技创新团队项目陕西省科技厅项目

82274347陕教[2019]90号2022SF-222

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(11)