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内容来源于J Ethnopharmacol 

基于血清代谢组学的毛冬青提取物对血瘀模型大鼠治疗作用的研究

中药毛冬青为冬青科植物毛冬青的根，具有清热解毒、活血通络的功效，常用于治疗心血管疾病，但毛冬青预防血瘀的作用机制尚不清楚。近期，中山大学金晶研究团队和广州中医药大学赵钟祥研究团队发表在“J Ethnopharmacol ”名为“The therapeutic effect of Ilex pubescens extract on blood stasis model rats according to serum metabolomics”的论文在中药毛冬青对大鼠急性血瘀预防作用及其机制研究方面取得进展。该研究团队将大鼠分为7组（对照组、模型组、阿司匹林治疗组、氯吡格雷治疗组和毛冬青高中低剂量治疗组），采用超高效液相色谱-四级杆飞行时间质谱对血清代谢产物进行了分析，并采用主成分分析法和正交偏最小二乘判别分析法相结合的多变量数据分析技术对差异变量进行了识别。研究结果显示中药毛冬青通过调节抗血小板聚集活性，纤维蛋白原浓度，凝血酶原时间和凝血酶时间等帮助大鼠对抗血瘀。该团队通过多变量数据分析法揭示了血清中18种差异生物标志物，其主要参与花生四烯酸代谢、甘油磷脂代谢、磷脂生物合成、胆汁酸生物合成等代谢途径，并发现在给与毛冬青的血瘀大鼠血清中，11种发生了显著的变化的生物标志物具有恢复正常的趋势。本研究提示中药毛冬青通过调节花生四烯酸和甘油磷脂代谢对大鼠血瘀有预防作用。

J Ethnopharmacol  2018;227:18-28 

doi:10.1016/j.jep.2018.08.026

The therapeutic effect of Ilex pubescens extract on blood stasis model rats according to serum metabolomics.

ABSTRACT

Ethnopharmacological relevance: Ilex pubescens Hook. et Arn (MDQ), a traditional Chinese herb, is used in the treatment of cardiovascular diseases. However, the mechanisms underlying the preventive effect of MDQ on blood stasis remain unclear.

Aim of the study：In this study, serum metabolomics integrated with a biochemical assay strategy were established to evaluate the preventive effect and mechanism of action of MDQ on rats with acute blood stasis.

Materials and methods: Forty-nine rats were divided into seven groups: the control group, model group, aspirin treatment group (30 mg/kg), clopidogrel treatment group (8 mg/kg) and three MDQ treatment groups (250, 500 and 1000 mg/kg). A hybrid quadrupole time of flight mass spectrometry (QTOF/MS) coupled to ultra-high-performance liquid chromatography (UPLC) was applied for profiling the serum metabolites. The multivariate data analysis techniques using unsupervised principal component analysis (PCA) and supervised orthogonal projections to latent structures discriminant analysis (OPLS-DA) were used for pattern recognition and distinguishing variabilities among groups.

Results: MDQ protected the rats against blood stasis, as evidenced by the restoration of the anti-platelet aggregation activity, fibrinogen concentration, prothrombin time, thrombin time, activated partial thromboplastin time, endothelial nitric oxide synthase, endothelin, thromboxane B2 and 6-keto-prostaglandin F1α. The combination of PCA and OPLS-DA revealed deviations in eighteen differential biomarkers in serum. The identified biomarkers were primarily engaged in the metabolic pathways including arachidonic acid metabolism, glycerophospholipid metabolism, phospholipid biosynthesis and bile acid biosynthesis. The levels of eleven biomarkers showed significant alterations and a tendency to be restored to normal values in MDQ-treated blood stasis rats. Moreover, a correlation network diagram was constructed to show the serum biomarkers perturbed by MDQ.

Conclusions: These results suggested that MDQ had preventive effects on blood stasis in rats via arachidonic acid metabolism and glycerophospholipid metabolism.

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