학술논문
当归-川芎药对改善脑缺血再灌注急性损伤的代谢组学机制分析 / Metabolomics mechanism study on the improvement of acute cerebral is-chemia/reperfusion injury by Danggui-Chuanxiong herb pair
Document Type
Academic Journal
Author
翟优; 李琨; 陈毓龙; 泥文娟; 纪秋如; 王晓艳; 张辉; 孟伟亭; 唐进法; 李伟霞; ZHAI You; LI Kun; CHEN Yulong; NI Wenjuan; JI Qiuru; WANG Xiaoyan; ZHANG Hui; MENG Weiting; TANG Jinfa; LI Weixia
Source
郑州大学学报（医学版） / Journal of Zhengzhou University(Medical Sciences). 58(6):757-763
Subject
Language
Chinese
ISSN
1671-6825
Abstract
目的:运用代谢组学方法探究当归-川芎药对抗脑缺血再灌注急性损伤的可能机制.方法:60 只雌性SD大鼠随机分成6 组,每组 10 只.DG、CX和GX组按 5 倍临床剂量给药当归、川芎、当归-川芎药对;NM组按照20 mg/(kg·d)灌胃尼莫地平片混悬液;假手术组和模型组大鼠灌胃等体积生理盐水;连续灌胃7d.除假手术组,其他5 组于第7 天采用线栓法制备大脑中动脉栓塞/再灌注(MCAO/R)损伤大鼠模型.再灌注 24h后,采集血清和脑组织标本,采用超高效液相色谱-四极杆-飞行时间质谱(UPLC-QTOF/MS)技术进行非靶向代谢组学检测,利用非监督主成分分析(PCA)、有监督型偏最小二乘-判别分析(PLS-DA)和正交偏最小二乘判别分析(OPLS-DA)筛选差异代谢物,并进行代谢通路注释.结果:假手术组和模型组血清和脑组织代谢轮廓存在明显差异(P<0.05),共筛选出与MCAO/R相关的嘌呤类、磷脂类、脂肪酸类等19 个潜在生物标志物,其中血清生物标志物5 个,脑组织生物标志物14 个.与当归-川芎药对治疗MCAO/R损伤密切相关的生物标志物有 11 个,主要与抗坏血酸与醛酸代谢、烟酸和烟酰胺代谢、甘油磷脂代谢、戊糖和葡糖醛酸的相互转化、柠檬酸循环等代谢通路有关.结论:当归-川芎药对可逆转脑缺血再灌注急性损伤大鼠的代谢紊乱,筛选出的内源性差异代谢物或可成为该药对治疗脑缺血再灌注急性损伤的潜在靶点.
Aim:To explore the possible mechanism of Danggui-Chuanxiong herb pair against acute cerebral ischemia/reperfusion injury.Methods:A total of 60 female SD rats were randomly allocated into 6 groups,with 10 rats in each group.DG,CX and GX groups were treated with 5 times of clinical dose of Danggui,Chuanxiong and Danggui-Chuanxiong herb pair,respectively;while NM group was treated with Nimodipine 20 mg/(kg·d);Sham group and the model group were giv-en the same volume of normal saline by gavage for 7 days.Except the Sham group,the middle cerebral artery occlusion/reperfusion(MCAO/R)model was established by wire embolism in the other 5 groups on the 7th day.After 24 hours of reperfusion,serum and brain tissue samples were collected,ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-QTOF/MS)technology was used to perform non-targeted metabolomics analysis,and en-dogenous differential metabolites were screened by combining unsupervised principal component analysis(PCA),supervised partial least squares discriminant analysis(PLS-DA),and orthogonal partial least squares discriminant analysis(OPLS-DA),and metabolic pathway analysis annotations were performed.Results:There were significant differences in the meta-bolic profiles of serum and brain tissue between sham group and model group(P<0.05).A total of 19 potential biomarkers related to the MCAO/R model,including purines,phospholipids,and fatty acids,were identified through screening.There were 5 serum biomarkers and 14 brain biomarkers.Among them,there were 11 biomarkers closely related to the treatment of MCAO/R injury with Danggui-Chuanxiong herb pair,mainly related to ascorbate and aldarate metabolism,nicotinate and nicotinamide metabolism,glycerophospholipid metabolism,pentose and glucuronate interconversions,citrate cycle,ect.Con-clusion:Danggui-Chuanxiong herb pair can reverse metabolic disorders of the rats with acute cerebral ischemia/reperfusion injury,and the screened endogenous differential metabolites may be potential target for the treatment.
Aim:To explore the possible mechanism of Danggui-Chuanxiong herb pair against acute cerebral ischemia/reperfusion injury.Methods:A total of 60 female SD rats were randomly allocated into 6 groups,with 10 rats in each group.DG,CX and GX groups were treated with 5 times of clinical dose of Danggui,Chuanxiong and Danggui-Chuanxiong herb pair,respectively;while NM group was treated with Nimodipine 20 mg/(kg·d);Sham group and the model group were giv-en the same volume of normal saline by gavage for 7 days.Except the Sham group,the middle cerebral artery occlusion/reperfusion(MCAO/R)model was established by wire embolism in the other 5 groups on the 7th day.After 24 hours of reperfusion,serum and brain tissue samples were collected,ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-QTOF/MS)technology was used to perform non-targeted metabolomics analysis,and en-dogenous differential metabolites were screened by combining unsupervised principal component analysis(PCA),supervised partial least squares discriminant analysis(PLS-DA),and orthogonal partial least squares discriminant analysis(OPLS-DA),and metabolic pathway analysis annotations were performed.Results:There were significant differences in the meta-bolic profiles of serum and brain tissue between sham group and model group(P<0.05).A total of 19 potential biomarkers related to the MCAO/R model,including purines,phospholipids,and fatty acids,were identified through screening.There were 5 serum biomarkers and 14 brain biomarkers.Among them,there were 11 biomarkers closely related to the treatment of MCAO/R injury with Danggui-Chuanxiong herb pair,mainly related to ascorbate and aldarate metabolism,nicotinate and nicotinamide metabolism,glycerophospholipid metabolism,pentose and glucuronate interconversions,citrate cycle,ect.Con-clusion:Danggui-Chuanxiong herb pair can reverse metabolic disorders of the rats with acute cerebral ischemia/reperfusion injury,and the screened endogenous differential metabolites may be potential target for the treatment.