基于1 H-NMR的丹七片对自发性高血压大鼠尿液代谢组学分析

Analysis of Danqi Tablets on Urine Metabolomics of Spontaneously Hypertension Rats Based on 1H-NMR

摘要:

目的：根据自发性高血压大鼠（SHR）和正常WKY大鼠尿液的代谢组学差异，研究丹七片对SHR血压及尿液中差异性代谢物的影响。方法：使用自发性高血压大鼠（SHR）和WKY大鼠，将SHR分为丹七片组（0.38 g·kg^-1），阿司匹林组（10 mg·kg^-1）和丹七片+阿司匹林组（0.38 g·kg^-1+10 mg·kg^-1）。给药前后每周连续监测大鼠尾动脉收缩压，每周收集大鼠24 h尿液。尿液样本进行¹H-NMR检测，通过模式识别分析的偏最小二乘法-判别分析（PLS-DA）和正交偏最小二乘法-判别分析（OPLS-DA）分析丹七片与阿司匹林对SHR尿液中差异性代谢物的影响。结果：药物干预4周后，各给药组大鼠血压均明显降低；SHR与WKY大鼠比较尿液中有21种主要差异性代谢物（丙氨酸，琥珀酸，α-酮戊二酸，柠檬酸，二甲胺，三甲胺，二甲基甘氨酸，赖氨酸，肌酸，胆碱，肌酸酐，氧化三甲胺，甜菜碱，牛磺酸，β-葡萄糖，苯乙酰甘氨酸，胍基乙酸，苯丙氨酸，马尿酸，1-甲基烟酰胺，尿囊素）。丹七片、阿司匹林、丹七片+阿司匹林均可使SHR尿液中差异性代谢物分布状态回归正常。结论：丹七片、丹七片+阿司匹林均可降低SHR血压，且可通过干预SHR尿液中与高血压发生相关的差异性代谢物分布状态来达到治疗高血压的作用。

Abstract:

Objective: According to urine metabonomics differences between spontaneously hypertensive rats (SHR) and WKY rats,to investigate effect of Danqi tablets on blood pressure and urine metabolomics of SHR. Method: SHR and WKY rats were used in the study.SHR were randomly divided into Danqi tablets group(dose of 0.38 g·kg^-1),aspirin group (10 mg·kg^-1),Danqi tablets+aspirin group (dose of 0.38 g·kg^-1 and 10 mg·kg^-1).Systolic blood pressure (SBP) of rat tail artery was constantly monitored before and after administration and rat urine in 24 hours was collected.All urine samples were detected by ¹H-NMR.Partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to discussed effect of Danqi tablets and aspirin on metabolites in urine of SHR. Result: Compared with the model group,blood pressure of all groups was significantly lower after 4 weeks.Compared with WKY rats, 21 kinds of different metabolites were found in SHR urine,they mainly included alanine,succinate,dimethylamine and so on.Danqi tablets,aspirin and Danqi tablets+aspirin all can make the distribution of a part of different metabolites in SHR urine back to normal. Conclusion: Danqi tablets and Danqi tablets+aspirin can lower the blood pressure of SHR,these two kinds of drugs can adjust distribution of relevant differetial metabolites associated with hypertension.