摘要
目的:应用代谢组学技术探讨克银丸对银屑病血热证大鼠模型血清代谢的影响,揭示其改善模型大鼠炎症反应的内在机制。方法:建立大鼠银屑病血热证模型,以克银丸灌胃4 w,观察大鼠体质量、摄食量、饮水量,肛温变化;HE染色观察大鼠背部皮肤的病理改变情况;通过Western blot法和qRT-PCR法检测皮损组织肿瘤坏死因子-α(TNF-α)、白介素(IL)-1β、IL-17A、IL-22、IL-23蛋白和mRNA的表达;采用超高效液相色谱与串联四级杆飞行时间质谱仪联用技术(UPLC-Q-TOF-MS/MS)进行大鼠血清代谢组学分析,探寻克银丸干预银屑病血热证大鼠的潜在生物标志物和相关代谢通路。结果:与正常对照组比较,模型对照组体质量、摄食量降低,饮水量、肛温升高,皮损组织可见明显病理改变,皮损组织TNF-α、IL-1β、IL-17A、IL-22、IL-23蛋白以及mRNA的表达明显上调(P<0.05或P<0.01);与模型对照组比较,克银丸3、9 g/kg组大鼠体质量、摄食量增加,饮水量、肛温降低,皮损状态减轻,皮损组织中TNF-α、IL-1β、IL-17A、IL-22、IL-23蛋白以及mRNA的表达下调(P<0.05或P<0.01);结合多元统计分析和在线数据库,正常对照组、模型对照组和克银丸9 g/kg组,共筛选出22个差异代谢物,主要富集到鞘脂代谢和色氨酸代谢等多个通路。结论:克银丸通过调节鞘脂代谢通路和色氨酸代谢通路对银屑病血热证大鼠具有较好的抗炎作用和修复皮肤屏障作用。
Objective:To investigate the effect of Keyin(克银)Pills on serum metabolism of psoriasis model rats with blood heat syndrome by metabolomics,and to reveal the internal mechanism of inflammatory response improvement in rats.Methods:A psoriasis rat model with blood heat syndrome was established.After the rats were administered Keyin Pills by gavage for 4 weeks,the following aspects were observed:the body weight,food intake,water intake,and rectal temperature,pathological changes in the dorsal skin by Hematoxylin-eosin(HE)staining,tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-17A,IL-22,IL-23 proteins,and mRNA expression levels in the skin lesions by Western blot and quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR),as well as serum metabolomics analysis by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS).All these aim to identify potential biomarkers and related metabolic pathways affected by Keyin Pills.Results:Compared with the normal control group,the TNF-α,IL-1β,IL-17A,IL-22,IL-23 protein,and mRNA expression were significantly upregulated in the model control group(P<0.05 or P<0.01).Compared with the model control group,the skin lesions were effectively alleviated in the Keyin Pill administration group,with the TNF-α,IL-1β,IL-17A,IL-22,IL-23 protein,and mRNA expression levels being significantly downregulated in skin lesions(P<0.05 or P<0.01).Combined with multivariate statistics and online databases,a total of 22 differential metabolites were screened out in the normal control group,model control group,and Keyin Pill administration group.The metabolites were mainly enriched in multiple pathways,including sphingolipid metabolism and tryptophan metabolism.Conclusion:Keyin Pills exert significant anti-inflammatory and skin barrier repair effects in psoriasis rats with blood heat syndrome by regulating the sphingolipid metabolism and tryptophan metabolism pathways.
作者
黄琳
孙慧娟
邓戈宇
王宇
高蕊
张萌萌
张振东
刘树民
HUANG Lin;SUN Huijuan;DENG Geyu;WANG Yu;GAO Rui;ZHANG Mengmeng;ZHANG Zhendong;LIU Shumin(Graduate School of Heilongjiang University of Chinese Medicine,Harbin 150040;Institute of Chinese Medicine,Heilongjiang University of Chinese Medicine,Harbin 150040)
出处
《中药药理与临床》
北大核心
2025年第10期32-37,共6页
Pharmacology and Clinics of Chinese Materia Medica
基金
国家重点研发计划-中医药现代化(编号:2022YFC3502100、2022YFC3502102、2022YFC3502102-04)。
关键词
克银丸
银屑病
血热证
炎症
血清代谢组学
鞘脂代谢通路
色氨酸代谢通路
Keyin Pills
Psoriasis
Blood heat syndrome
Inflammation
Serum metabolomics
Sphingolipid metabolic pathway
Tryptophan metabolic pathway
