基于代谢组学研究蒙药胡日查-6干预豚鼠过敏性鼻炎的作用机制  

Study on the Mechanism of Mongolian Medicine Huricha-6 on Guinea Pigs with Allergic Rhinitis Based on Metabolomics

作　　者：苏日古格 乌日柴夫 吉日木巴图[1] 李花[1] 韩额尔德木图 孟永梅[1] SU Riguge;WU Richaufu;JI Rimubatu;LI Hua;HAN Eerdemutu;MENG Yongmei(Inner Mongolia Medical University,Hohhot Inner Mongolia 010110,China)

机构地区：[1]内蒙古医科大学,内蒙古呼和浩特010110

出　　处：《中医药导报》2025年第2期7-12,共6页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家民委-教育部蒙医药研发工程重点实验室开放基金项目(MDK2020015);内蒙古医科大学校级重点项目(YKD2024 ZD008)。

摘　　要：目的:通过豚鼠血浆代谢组学研究揭示蒙药胡日查-6干预过敏性鼻炎(AR)的可能作用机制并进行实验验证。方法:将54只SPF级豚鼠随机分为空白对照组(n=12)、模型组(n=14)、蒙药组(n=14)及阳性对照组(n=14),除空白对照组外,其余各组豚鼠通过卵清蛋白(OVA)诱导AR豚鼠模型,相应药物治疗6周,采用超高效液相色谱联用仪(UHPLC-OE-MS)检测各组豚鼠血浆代谢物,通过多元统计分析、变量投影重要性值(VIP)和P值筛选各组间差异代谢物,并进行代谢通路分析;采用蛋白免疫印迹法(Western blotting)检测豚鼠肺组织肿瘤坏死因子-α(TNF-α)、酸性鞘磷脂酶(ASM)及核因子κB(NF-κB)p65蛋白表达。结果:与空白对照组比较,模型组鉴定出85个差异代谢物;与模型组比较,蒙药组鉴定出33个差异代谢物,差异代谢物主要富集在癌症中的胆碱代谢、甘油磷脂代谢、鞘脂信号通路等32条代谢通路;阳性对照组鉴定出81个差异代谢物,主要富集在癌症中的胆碱代谢、甘油磷脂代谢、嘧啶代谢等43条通路。综合网络药理学、代谢组学KEGG通路,两者取交集后,共得到9条通路。模型组豚鼠肺组织TNF-α、ASM及NF-κB p65蛋白相对表达量高于空白对照组(P<0.01);蒙药组、阳性对照组豚鼠肺组织TNF-α、ASM及NF-κB p65蛋白相对表达量均低于模型组(P<0.05)。结论:胡日查-6可能通过影响鞘脂信号通路发挥干预AR的作用。Objective:To reveal the possible mechanism of Huricha-6 in the treatment of allergic rhinitis(AR)through the study of plasma metabolomics in guinea pigs and to verify it experimentally.Methods:The 54 SPF grade guinea pigs were randomly divided into blank control group(n=12),model group(n=14),Mongolian medicine group(n=14)and positive control group(n=14).Except the blank control group,the AR guinea pig model of the other groups was induced by ovalbumin and treated with corresponding drugs for 6 weeks.The plasma metabolites of the guinea pigs in each group were detected by UHPLC-OE-MS.The differential metabolites were screened by multivariate statistical analysis,projected importance value(VIP)and P-value,and the metabolic pathways were analyzed.Then,the metabolic pathway analysis was carried out.Western blotting was used to detect the expressions of TNF-α,ASM and NF-κB p65 proteins in lung tissues of guinea pigs in each group.Results:Compared with the blank control group,85 different metabolites were identified in the model group.Compared with the model group,33 kinds of differential metabolites were identified in Mongolian medicine group,and the differential metabolites were mainly concentrated in 32 metabolic pathways such as choline metabolism,glycerol phospholipid metabolism and sphingolipid signaling pathway.A total of 81 different metabolites were identified in positive control group,mainly concentrated in 43 pathways such as bile metabolism in cancer,glycerol phospholipid metabolism,and pyrimidine metabolism.According to the combination of network pharmacology and metabolomics KEGG pathway,9 pathways were obtained after the intersection of the two pathways.The model group showed higher expressions of TNF-α,ASM and NF-κB p65 in lung tissue than blank control group(P<0.01).The Mongolian medicine group and positive control group showed lower expressions of TNF-α,ASM and NF-κB p65 protein than model group(P<0.05).Conclusion:Huricha-6 may interfere with AR by affecting sphingolipid signaling pathway.

关 键 词：过敏性鼻炎 胡日查-6 蒙药 豚鼠 血浆代谢组学 作用机制 

分 类 号：R285.5[医药卫生—中药学]