基于血清代谢组学探讨赤芍标准汤剂与配方颗粒对热毒血瘀证大鼠的效应机制  

Serum metabolomics reveals effects of standard decoction and formula granules of Paeoniae Radix Rubra on rat model of heat toxin and blood stasis

作　　者：黄晓丹[1] 黄雪君 甘海宁 肖观林 王灵芝 龚淼玲 赵自明 HUANG Xiao-dan;HUANG Xue-jun;GAN Hai-ning;XIAO Guan-lin;WANG Ling-zhi;GONG Miao-ling;ZHAO Zi-ming(the Fifth Clinical College of Guangzhou University of Chinese Medicine,Guangzhou 510095,China;Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine,Guangzhou 510095,China;Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Research and Development,Guangzhou 510095,China)

机构地区：[1]广州中医药大学第五临床医学院,广东广州510095 [2]广东省中医药工程技术研究院,广东广州510095 [3]广东省中医药研究开发重点实验室,广东广州510095

出　　处：《中国中药杂志》2024年第19期5181-5192,共12页China Journal of Chinese Materia Medica

基　　金：国家“重大新药创制”科技重大专项(2018ZX09301011-002);广东省第二中医院科研创新基金项目(SEZYY2023A04)。

摘　　要：比较赤芍标准汤剂及其配方颗粒对热毒血瘀证大鼠的调节作用及代谢调控机制。将SD大鼠随机分为对照组、模型组、赤芍标准汤剂组、赤芍配方颗粒组。大鼠给药14 d后皮下注射角叉菜胶及腹腔注射细菌脂多糖复制热毒血瘀证模型,检测大鼠肛温、凝血四项及血小板聚集率(platelet aggregation,PAG);检测血清血栓素B_(2)(thromboxane B_(2),TXB_(2))、6-酮前列腺素F1α(6-ketone-prostaglondin F1α,6-keto-PGF1α)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、血管性血友病因子(von Willebrand factor,vWF)、内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)、内皮素-1(endothelin-1,ET-1)水平;采用超高效液相色谱串联四极杆飞行时间质谱(UPLC-Q/TOF-MS)结合多元统计分析筛选血清差异代谢物,进行KEGG通路富集分析及比较。结果显示,赤芍标准汤剂及配方颗粒均能降低模型大鼠体温、减少血小板聚集及改善凝血功能,可能通过减轻炎症和调节血管功能来改善大鼠热毒血瘀状态。对大鼠血清代谢组学进行分析,与模型组比较,赤芍标准汤剂组和赤芍配方颗粒组分别回调了15、65个差异代谢物,代谢通路富集分析显示,赤芍标准汤剂通过影响α-亚麻酸代谢、初级胆汁酸生物合成、亚油酸代谢和苯丙氨酸代谢4条关键代谢通路发挥作用;赤芍配方颗粒通过影响α-亚麻酸代谢、柠檬酸盐循环(TCA循环)、嘌呤代谢、乙醛酸和二羧酸代谢4条关键代谢通路发挥作用。该研究表明赤芍标准汤剂及配方颗粒均对热毒血瘀证有改善作用,二者效果相当,均能通过α-亚麻酸分解代谢起治疗作用,为赤芍配方颗粒的临床应用提供了一定科学依据。This study aims to compare the effects and mechanisms of the standard decoction and formula granules of Paeoniae Radix Rubra in regulating the metabolism in the rat model of heat toxin and blood stasis.SD rats were randomized into control,model,standard decoction,and formula granules groups.After 14 days of administration,the rats in the latter three groups were subjected to subcutaneous injection with carrageenan and intraperitoneal injection with bacterial lipopolysaccharide for the modeling of heat toxin and blood stasis.The anal temperature,coagulation indexes,platelet aggregation(PAG),serum levels of thromboxane B_(2)(TXB_(2)),6-ketone-prostaglondin F1α(6-keto-PGF1α),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),von Willebrand factor(vWF),endothelial nitric oxide synthase(eNOS),and endothelin-1(ET-1)were measured.The metabolites in rat serum were identified by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS).Multivariate statistical analysis was performed to screen the differential metabolites,which were then subjected to the KEGG pathway enrichment analysis.The results showed that the standard decoction and formula granules of Paeoniae Radix Rubra improved the state of model rats by lowering the body temperature,inhibiting inflammation,reducing PAG,delaying coagulation,and regulating the vascular function.The metabolomics analysis screened out 15 and 65 differential metabolites in the standard decoction and formula granules groups,respectively,compared with the model group.The enrichment analysis of the differential metabolites showed that the standard decoction of Paeoniae Radix Rubra exerted effects by affecting four key metabolic pathways:α-linolenic acid metabolism,primary bile acid biosynthesis,linoleic acid metabolism,and phenylalanine metabolism.The formula granules of Paeoniae Radix Rubra exerted effects by affecting four key metabolic pathways:α-linolenic acid metabolism,citrate cycle(tricarboxylic acid cycle),purine metabolism,a

关 键 词：赤芍 配方颗粒 标准煎剂 热毒血瘀证 代谢组学 

分 类 号：R285.5[医药卫生—中药学]