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基于超高效液相色谱-质谱联用技术对冠心病痰证或血瘀证患者血清代谢组学及方剂-证型对应关系的研究

Study of Serum Metabonomics and Formula-Pattern Correspondence in Coronary Heart Disease Patients Diagnosed as Phlegm or Blood Stasis Pattern Based on Ultra Performance Liquid Chromatography Mass Spectrometry.

作者信息

Lu Xiao-Yan, Xu Hao, Zhao Tie, Li Geng

机构信息

Department of Integrative Cardiology, China-Japan Friendship Hospital, Beijing, 100029, China.

Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.

出版信息

Chin J Integr Med. 2018 Dec;24(12):905-911. doi: 10.1007/s11655-018-2564-7. Epub 2018 Jun 8.

Abstract

OBJECTIVES

To study the characteristics of serum metabonomics in coronary heart disease (CHD) patients diagnosed as phlegm or blood stasis pattern and explore effects of formula-pattern correspondence treatment.

METHODS

A total of 102 stable CHD patients were enrolled and divided into phlegm group (P group, n=52) and blood stasis group (BS group, n=50) according to pattern identifification. Gualou Xiebai Banxia Decoction (, GXBD) and Xuefu Zhuyu Decoction (, XZD) were used as drug interventions. Relevant indicators of metabonomics were observed by ultra performance liquid chromatography mass spectrometry (UPLC-MS) and pattern recognition.

RESULTS

Levels of amino acids and phosphatidylethanolamine (PE) in the CHD group were much higher than those in healthy control group, while the levels of unsaturated fatty acids, sphingosine, Lyso, phosphatidylcholine (PC) were signifificantly lower (P<0.01). Most of the differential metabolites between the CHD and the healthy groups were also common metabolites of phlegm and blood stasis. 7(Z), 10(Z)-hexadecadienoic acid and DPA were decreased in the P group and increased in the BS group. According to the quantity of retraced metabolites, improvement in metabonomics by formula-pattern correspondence was superior to that without correspondence in the BS group. Based on the varieties of metabolites, GXBD could improve the levels of docosapentaenoic acid (DPA), sphingomyelin (SM) (d34:1), and L-Lactic acid and XZD could ameliorate the levels of sphingosine and Vit E in the P group. In the BS group, GXBD could improve vitamin E level and XZD could make improvements in the levels of octadecanoic acid, phosphoglycerol, and SM (d34:1).

CONCLUSIONS

Phlegm and blood stasis in CHD patients present specifific differential metabolites, and share common metabolites. Remarkable differences have been displayed in pathological properties and severity of phlegm and blood stasis. Patients with phlegm are more likely to have lipid metabolism disorders. However, in patients with blood stasis, problems mainly lie in glucose, protein and fat metabolism and the injury of vascular cell membrane is relatively severe. The metabolic disorder is more complicated in blood stasis pattern than that in phlegm pattern. Compared with non-correspondence, improvement of differential metabolites is more comprehensive and targeted in formulapattern correspondence with a better effect.

摘要

目的

研究冠心病(CHD)痰证和血瘀证患者的血清代谢组学特征,探讨方证对应治疗的效果。

方法

纳入102例稳定型CHD患者,根据辨证分为痰证组(P组,n = 52)和血瘀组(BS组,n = 50)。以瓜蒌薤白半夏汤(GXBD)和血府逐瘀汤(XZD)作为药物干预。采用超高效液相色谱-质谱联用(UPLC-MS)和模式识别技术观察代谢组学的相关指标。

结果

CHD组氨基酸和磷脂酰乙醇胺(PE)水平显著高于健康对照组,而不饱和脂肪酸、鞘氨醇、溶血磷脂、磷脂酰胆碱(PC)水平显著降低(P<0.01)。CHD组与健康组之间的大多数差异代谢物也是痰证和血瘀证的共同代谢物。7(Z),10(Z)-十六碳二烯酸和二十二碳五烯酸(DPA)在P组降低,在BS组升高。根据回溯代谢物数量,方证对应在BS组对代谢组学的改善优于非对应。基于代谢物种类,GXBD可提高P组二十二碳五烯酸(DPA)、鞘磷脂(SM)(d34:1)和L-乳酸水平,XZD可改善鞘氨醇和维生素E水平。在BS组,GXBD可提高维生素E水平,XZD可改善十八烷酸、磷酸甘油和SM(d34:1)水平。

结论

CHD患者痰证和血瘀证存在特定的差异代谢物,且有共同代谢物。痰证和血瘀证在病理性质和严重程度上有显著差异。痰证患者更易出现脂质代谢紊乱。然而,血瘀证患者问题主要在于糖、蛋白质和脂肪代谢,血管细胞膜损伤相对严重。血瘀证的代谢紊乱比痰证更复杂。与非对应相比,方证对应对差异代谢物的改善更全面、有针对性,效果更好。

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