扩散编辑实验分析慢性心肌缺血血瘀证模型血清脂类代谢变化

目的:研究Ameriod环所致冠心病(慢性心肌缺血)小型猪的血清脂类代谢物谱群的变化,并通过对冠心病心肌缺血模型动物代谢物组的共性分析和特异表达物的探索,寻找血瘀证可能的生物学基础。方法:采用左冠状动脉前降支近端放置Ameroid缩窄环的方法建立慢性心肌缺血模型。术后0-12周对动物采集包括舌象在内的详细四诊信息,并结合血液流变学等方法确立中医血瘀证证候,用Varian UnityInova 600 M超导傅立叶变化核磁共振(NMR)波谱仪检测血清。扩散编辑实验(LED)分析脂类代谢变化情况,自由感应衰减信号经过32k傅立叶变换转为一维NMR谱图。图谱进行分段积分,每段为0.01ppm,将积分数据归一化后,利用Simca-P 11.5软件包进行模式识别主成份(PCA)分析。结果:该方法制备的模型4周确立为稳定的慢性心肌缺血血瘀证模型。基于模式识别技术的主成份分析(PCA)清晰的把模型组与假手术组动物分别开来,LED图谱的主成分分析、动物代谢谱各不相同。其中脂类代谢产物甘油(Glycerol)、低密度脂蛋白(LDL)和极低密度脂蛋白(VLDL)、胆碱以及糖代谢葡萄糖、乳酸浓度上升,高密度脂蛋白(HDL)等含量降低。结论:在血瘀证早期葡萄糖代谢紊乱和脂类代谢障碍相互影响,最终加重并恶化了冠心病血瘀证的进程,代谢组学结合模式识别技术能有效判别证候之间的差异,为中医证候规范化提供新的研究方法。

Experimental study on lipid metabolism disorder in coronary heart disease(chronic myocardial ischemia) with syndrome of blood stasis based on the NMR metabolomics

Objective:To study coronary heart disease(chronic myocardial ischemia) with syndrome of blood stasis caused by ameriod ring and its changes in the serum lipid metabolite profiling so as to reveal the biological features of the syndrome of syndrome of blood stasis,and to examine potential application of metabolomic analysis in studies of syndromes in Traditional Chinese medicineTCM.Methods:Ameroid constriction ring was placed on the left anterior descending coronary artery to prepare the chronic myocardial ischemia model.The four diagnostic information was collected from 0 to 12 weeks after operation.Hemorheology was applied to established blood stasis syndrome,Varian UnityInova 600 M superconducting Fourier(nuclear magnetic resonance,NMR) spectrometer was used to detect the serum.Free induction decay signal was transferred into one-dimensional NMR spectra by 32 k.Longitudinaleddy-delay(LED) to analyze changes of lipid metabolism;the normalized data is carried out to take PCA analysis by Simca-P 11.5 software package.Results:The principal component analysis(PCA) of serum LED spectrum and metabolic spectrum in two groups are significantly different.Compared with the sham group,endogenous metabolites in the serum in model group have these changes:the concentration of lipid metabolites such as LDL,VLDL,glycol,choline,lactate,glucose rise,the levels of high density lipoprotein(HDL) decline.Conclusion:Significant differences in metabolic spectrum were existed in syndrome of blood stasis and non-blood stasis.Glucose metabolism and lipid metabolism disorders in early stage of blood stasis,both reinforce each other,resulting a deterioration of the process in coronary artery disease;these metabolites pattern may be used as clinical diagnosis and treatment of coronary artery disease indicators,and also can provide a new approach to objective research for the syndrome.