摘要
目的探讨化痰活血通络方对动脉粥样硬化(As)小鼠血脂的作用及其潜在脂质生物标志物的影响。方法高脂饮食喂养ApoE-/-雄性小鼠18周建立As模型,用化痰活血通络方治疗4周后,生化分析小鼠血脂水平;苏木精-伊红(HE)染色观察主动脉和肝脏组织损伤情况;基于高效液相色谱-高分辨质谱(LC-MS)测定As的脂质标志物建立肝脏脂质谱。正交偏最小二乘法判别分析(OPLS-DA)进行生物标志物筛选。KEGG数据库进行的代谢通路注释来表征化痰活血通络方治疗As小鼠潜在脂质生物标志物及生物学效应。结果与空白组比较,模型组总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)升高,高密度脂蛋白胆固醇(HDL-C)降低;与模型组比较,各给药组小鼠TG、TC、LDL含量降低,HDL含量升高,差异均有统计学意义。LC-MS脂质组学共鉴定了509个As潜在的生物标志物,化痰活血通络方能够逆转其中99种生物标志物来促使机体恢复到正常趋势,主要属于三酰基甘油(TG)类、磷脂酰乙醇胺(PE)类、二酰基甘油(DG)类、磷脂酰胆碱(PC)类、前列腺素(PG)类、鞘磷脂(SM)类、心磷脂(CL)类、磷脂肌醇(PI)类、磷脂酰基丝氨酸(PS)类和神经酰胺(Cer)类,分别由甘油磷脂代谢、鞘脂代谢、亚油酸代谢、α-亚麻酸代谢、甘油酯代谢、花生四烯酸代谢通路调节。结论化痰活血通络方具有良好治疗效果,通过调节脂质生物标志物和脂质组学引导的生化分析途径来预防动脉粥样硬化。
Objective To investigate the effect of Huatan Huoxue Tongluofang(QF)on blood lipids in atherosclerotic(As)mice and its potential lipid biomarkers.Methods High-fat diet fed ApoE-/-male mice were fed for 18 weeks to establish an As model,and after four weeks of treatment with QF,lipid levels were analyzed biochemically;hematoxylin-eosin(HE)staining was performed to observe aortic and liver tissue damage;liver lipid profiles were established by determining lipid markers of As based on high performance liquid chromatography-high resolution mass spectrometry(LC-MS).Orthogonal partial least squares discriminant analysis(OPLS-DA)was performed for biomarker screening.metabolic pathway annotation by KEGG database was performed to characterize potential lipid biomarkers and biological effects in QF-treated AS mice.Results Compared with the NC group,total cholesterol(TC),triglycerides(TG)and low-density lipoprotein cholesterol(LDL-C)were increased and high-density lipoprotein cholesterol(HDL-C)was decreased in the model group.In comparison to the model group,TG,TC and LDL levels were decreased and HDL levels were increased in each of the doing groups,and the differences were found to be statistically significant.A total of 509 potential biomarkers of As were identified by LC-MS lipidomics,and the QF was able to reverse 99 of these biomarkers to induce the body to return to normal trend,mainly belonging to triacylglycerol(TG),phosphatidylethanolamine(PE),diacylglycerol(DG),phosphatidylcholine(PC),prostaglandin(PG),sphingomyelin(SM),cardiolipin(CL),phosphatidylinositol(PI),phosphatidylserine(PS)and ceramide(Cer),cardiolipin(CL),phosphatidylinositol(PI),phosphatidylserine(PS),and ceramide(Cer),which are regulated by glycerophospholipid metabolism,sphingolipid metabolism,linoleic acid metabolism,α-linolenic acid metabolism,glycerol ester metabolism,and arachidonic acid metabolism pathways,respectively.Conclusion The QF may improve As by regulating lipid pathways such as glycerophospholipid metabolism.
作者
程璇
萧闵
曾祥法
王武胜
叶焰
蔚文垚
葛春蕾
CHENG Xuan;XIAO Min;ZENG Xiang-fa;WANG Wu-sheng;YE Yan;YU Wen-yao;GE Chun-lei(Hubei University of Chinese Medicine,Wuhan Hubei 430065,China)
出处
《时珍国医国药》
CAS
CSCD
北大核心
2024年第2期323-330,共8页
Lishizhen Medicine and Materia Medica Research
基金
国医大师传承工作室建设项目【国中医药办人教函(2018)119号】
国家自然科学基金青年基金(82104704)。