基于^(1)H NMR代谢组学研究黄芩醇提物改善CFA致大鼠炎性疼痛的作用机制  

Research on the mechanisms of ethanol extract of Scutellaria baicalensis Georgi in improving CFA-induced inflammatory pain rats based on^(1)H NMR metabolomics

作　　者：赵锦霞 秦雪梅[1,2,3] 赵靖 高丽 ZHAO Jin-xia;QIN Xue-mei;ZHAO Jing;GAO Li(Modern Research Center for Traditional Chinese Medicine,Shanxi University,Taiyuan 030006,China;The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,Taiyuan 030006,China;The key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province,Taiyuan 030006,China;Wolfson Institute for Biomedical Research,University College London,London,UK)

机构地区：[1]山西大学中医药现代研究中心,山西太原030006 [2]化学生物学与分子工程教育部重点实验室,山西太原030006 [3]地产中药功效物质研究与利用山西省重点实验室,山西太原030006 [4]英国伦敦大学学院医学院Wolfson生物医学研究所,伦敦

出　　处：《药学学报》2023年第7期1922-1930,共9页Acta Pharmaceutica Sinica

基　　金：地产中药功效物质研究与利用山西省重点实验室(202105D121009).

摘　　要：本文旨在基于^(1)H NMR代谢组学技术,考察黄芩醇提物(ethanol extract of Scutellaria baicalensis Georgi,SGE)对完全弗氏佐剂(complete Freund’s adjuvant,CFA)诱导的炎性疼痛大鼠足趾中内源性代谢物的影响,为揭示SGE改善炎性疼痛的作用及机制提供依据。本实验获得山西大学伦理委员会的批准(批准号:SXULL2022062)。通过大鼠足底皮下注射CFA(0.1 mL)造成炎性疼痛模型,考察低、中、高剂量SGE(1.5、3、6 g·kg^(-1))改善炎性疼痛的作用和机制。通过测定机械压痛阈值(mechanical nociceptive thresholds,MNTs)评价SGE改善炎性疼痛的药效;采用Western blot检测SGE对环氧合酶-2(cyclooxygenase-2,COX-2)、核因子κB(nuclear factor kappa-B,NF-κB)和磷酸化NF-κB(phospho-NF-κB,p-NF-κB)蛋白表达的影响;采用^(1)H NMR代谢组学技术分析SGE对炎性疼痛大鼠足趾中内源性代谢物的调节作用。结果显示SGE(6 g·kg-1)能显著缓解CFA诱导的炎性疼痛,显著抑制COX-2、NF-κB和p-NF-κB蛋白表达,并能显著回调8种差异代谢物的改变,如甘氨酸、谷氨酰胺、琥珀酸、磷酸胆碱等;共涉及7条代谢通路如甘氨酸、丝氨酸和苏氨酸代谢,丙氨酸、天冬氨酸和谷氨酸代谢,乙醛酸和二羧酸代谢,谷胱甘肽代谢,甘油磷脂代谢等。结果表明,SGE可能通过调控NF-κB信号通路和代谢异常缓解炎性疼痛。The purpose of this study was to investigate the effects of ethanol extract of Scutellaria baicalensis Georgi(SGE)on endogenous metabolites in toes of rats with inflammatory pain induced by complete Freund's adjuvant(CFA)based on^(1)H NMR metabolomics,which would provide foundation for revealing the effects and mechanisms of SGE in improving inflammatory pain.This animal experiment was approved by the Committee on the Ethics of Animal Experiments of Shanxi University(SXULL2022062).The rats model of inflammatory pain was induced by subcutaneous injection of CFA(0.1 mL),and the effect of low,medium and high doses of SGE(1.5,3,6 g·kg^(-1))on inflammatory pain were explored.The effects of SGE on relieving inflammatory pain was evaluated by mechanical nociceptive thresholds(MNTs)test.Western blot was used to detect the effects of SGE on protein expression of cyclooxygenase-2(COX-2),nuclear factor kappa-B(NF-κB)and phospho-NF-κB(p-NF-κB).^(1)H NMR metabolomics was used to analyze the regulatory effects of SGE on endogenous metabolites in the toes of rats with inflammatory pain.The results showed that SGE(6 g·kg-1)could significantly relieve CFA-induced inflammatory pain,and also notably inhibit the protein expression of COX-2,NF-κB and p-NF-κB.SGE could markedly reverse the changes of 8 differential metabolites,such as glycine,glutamine,succinate,phosphorylcholine,etc.The metabolites were involved in eight metabolic pathways,such as glycine,serine and threonine metabolism,alanine,aspartate and glutamate metabolism,glyoxylate and dicarboxylate metabolism,glutathione metabolism,glycerophospholipid metabolism.These results suggest that SGE may relieve inflammatory pain by regulating NF-κB signaling pathway and metabolic abnormality.

关 键 词：黄芩醇提物 完全弗氏佐剂 炎性疼痛 代谢组学 作用机制 

分 类 号：R917[医药卫生—药物分析学]