钩藤提取液对自发性高血压大鼠尿液代谢组学的影响

Effects of Guoteng (Uncaria Rhynchophylla) Extracting Solution on Urine Metabolomics in Spontaneously Hypertensive Rats

目的探讨钩藤的降血压作用及可能作用机制。方法 18只自发性高血压(SHR)大鼠随机分为钩藤组和模型组各9只,9只Wistar大鼠作为正常组。钩藤组大鼠给予钩藤提取液10. 001 g/(kg·d)灌胃,模型组和正常组给予2 ml生理盐水灌胃,每日1次,持续4周。分别于实验0、1、2、3、4周时测定各组大鼠收缩压和舒张压,于实验4周时基于高效液相色谱-飞行时间质谱(HPLC-TOF/MS)技术,分析各组大鼠尿液代谢标志物的变化。结果模型组和钩藤组在0、1、2、3、4周时收缩压和舒张压均明显高于同时间点正常组(P <0. 01)。与模型组同时间点比较,钩藤组收缩压在2、3、4周时降低(P <0. 05);并且钩藤组在4周时收缩压和舒张压均较本组0、1、2、3周时降低(P <0. 05或P <0. 01)。共筛选出12个差异代谢标志物,分析发现钩藤干预后存在雄激素与雌激素代谢、α-亚麻酸和亚油酸代谢、精氨酸与脯氨酸代谢上调,花生四烯酸代谢、部分鞘脂代谢及色氨酸代谢下调。结论钩藤具有良好的降压效果,对一氧化氮的调控是其发挥降压作用的重要环节。

Objective To explore the anti-hypertensive effect and possible mechanism of Guoteng(Uncaria Rhynchophylla).Methods A total of 18 spontaneously hypertensive(SHR)rats were equally divided into a Guoteng group and a model group,and 9 Wistar rats were selected as the normal group.The rats in the Guoteng group were given 10.001 g/(kg·d)of the extracting solution of Guoteng(Uncaria Rhynchophylla),and the rats in the model group and the normal group were given 2 ml of normal saline,and were intragastrically administered once a day for 4 weeks.Systolic and diastolic blood pressure were measured in each group after treated 0,1,2,3,and 4 weeks.The changes of urine metabolic markers in each group were analyzed by high performance liquid chromatography with time-of-flight mass spectrometry(HPLC-TOF/MS)after 4 weeks.Results The systolic and diastolic blood pressures of the model group and the Guoteng group were significantly higher than those of the normal group in 0,1,2,3,and 4 weeks(P<0.01).Compared with the model group,the systolic blood pressure of the Guoteng group was decreased in 2,3,and 4 weeks(P<0.05),and the systolic and diastolic blood pressures of the Guoteng group were lower in 4 weeks than those in the 0,1,2 and 3 weeks(P<0.05 or P<0.01).A total of 12 distinctive biomarkers were screened,and analysis showed that the androgen and estrogen metabolism,α-linolenic acid and linoleic acid metabolism,arginine and proline metabolism up-regulation,arachidonic acid metabolism,sphingolipid metabolism,and tryptophan metabolism were down-regulated.Conclusion Guoteng(Uncaria Rhynchophylla)has a good antihypertensive effect,and an important part of its antihypertensive effect is the regulation of nitric oxide.