复方钩藤降压解郁方对高血压并发抑郁症大鼠的药效作用及物质基础

The Pharmacodynamics of Fufang Gouteng Jiangya Jieyu Prescription(复方钩藤降压解郁方)on Hypertension Complicated with Depression in Rats and Its Material Basis

目的:探讨复方钩藤降压解郁方对高血压并发抑郁症大鼠模型的药效作用及物质基础。方法:将20只SHR大鼠按随机数字表法分为模型组和复方钩藤降压解郁方组,每组10只。10只SD大鼠作为正常对照组。除正常对照组外,其余两组大鼠复制高血压并发抑郁症模型。给药干预后,测量各组大鼠血压变化情况,并通过Open-field实验、新奇摄食实验和糖水偏好实验,观察各组大鼠的抑郁症状,采用ELISA法检测大鼠海马组织中IL-1β、IL-6的水平。采用超高效液相色谱-四极杆-飞行时间质谱(UPLC-Q-TOF-MS)对复方钩藤降压解郁方的化学成分进行定性分析。结果:与正常对照组比较,模型组大鼠血压明显升高(P<0.01),自主活动减少、摄食潜伏期延长、糖水偏好程度降低(P<0.05或P<0.01),海马炎症因子IL-1β、IL-6水平明显升高(P<0.05)。与模型组比较,复方钩藤降压解郁方组大鼠血压在给药后明显降低(P<0.01),自主活动能力增多、摄食潜伏期缩短、糖水偏好程度升高(P<0.05或P<0.01),海马炎症因子IL-1β、IL-6水平明显降低(P<0.05)。采用UPLC-Q-TOF-MS鉴定出了复方钩藤降压解郁方中51个化学成分,主要包括黄酮类、糖苷类、苯丙素类、二萜类、生物碱类、酚酸及其酯类等,并对各成分的药材来源进行归属。结论:复方钩藤降压解郁方能明显降低高血压并发抑郁症模型大鼠的血压,改善其抑郁症状,下调其海马炎症因子IL-1β、IL-6的含量。利用UPLC-Q-TOF-MS正负离子流图综合分析了复方钩藤降压解郁方的化学成分,为其药效和物质基础的研究提供了实验依据。

Objective:To investigate the pharmacodynamic effect and material basis of Fufang Gouteng Jiangya Jieyu Prescription on the rat model of hypertension complicated with depression.Methods:A total of 20 SHR rats were randomly divided into model group and Fufang Gouteng Jiangya Jieyu Prescription group,with 10 rats in each group.10 SD rats served as normal control group.Except for the normal control group,the other two groups of rats replicated the model of hypertension complicated with depression.After the drug intervention,the blood pressure changes of the rats in each group were measured,and the depressive symptoms of the rats in each group were observed through the Open-field experiment,the novel feeding experiment and the sugar water preference experiment.The levels of IL-1βand IL-6 in rat hippocampus were detected by ELISA.The chemical constituents of Fufang Gouteng Jiangya Jieyu Prescription were qualitatively analyzed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS).Results:Compared with the normal control group,the blood pressure of rats in the model group was significantly increased(P<0.01),the autonomic activity was reduced,the feeding latency was prolonged,and the preference for sugar and water was reduced(P<0.05 or P<0.01).The levels of IL-1βand IL-6 in the hippocampus were significantly increased(P<0.05).Compared with the model group,the blood pressure of rats in the Fufang Gouteng Jiangya Jieyu Prescription group was significantly decreased after administration(P<0.01),the ability of independent activity was increased,the feeding latency was shortened,and the preference for sugar and water was increased(P<0.05 or P<0.01).The levels of IL-1βand IL-6 in the hippocampus were significantly decreased(P<0.05).UPLC-Q-TOF-MS was used to identify 51 chemical constituents in Fufang Gouteng Jiangya Jieyu Prescription,including flavonoids,glycosides,phenylpropanoids,diterpenoids,alkaloids,phenolic acids and their esters etc.,and attribution of the source of medicinal materials for each constituents.Conclusion:Fufang Gouteng Jiangya Jieyu Prescription can significantly reduce the blood pressure,improve the symptoms of depression,and down-regulate the levels of IL-1βand IL-6 in the hippocampus of rats with hypertension complicated by depression.UPLC-Q-TOF-MS positive and negative ion flow diagrams were used to comprehensively analyze the chemical constituents of Fufang Gouteng Jiangya Jieyu Prescription,which provided experimental basis for the study of its efficacy and material basis.