复方菊明与硝苯地平联用对老年自发性高血压大鼠血压及血管活性物质的影响

Effect of Compound Juming Combined with Nifedipine on Blood Pressure and Vasoactive Substances in Aged SHR Rats

[目的]研究复方菊明与硝苯地平联用对老年自发性高血压大鼠（SHR）血压和血管活性物质的影响。[方法]采用14月龄老年SHR,连续灌胃8周,于第4、6、8周测量收缩压（SBP）、舒张压（DBP）和平均动脉压（MBP）,末次给药后腹腔取血检测内皮素-1（ET-1）、降钙素基因相关肽（CGRP）、一氧化氮（NO）、血栓素B2（TXB2）、6-酮-前列腺素F1（α6-keto-PGF1α）、纤溶酶原激活物抑制因子-1（PAI-1）等指标。[结果]与模型组相比,硝苯地平（6mg.kg-）1能显著降低老年SHR的SBP、MBP（P〈0.01）,第6周起明显降低DBP（P〈0.05）,降低血浆ET-1（P〈0.05）,升高血清NO（P〈0.05）,对血浆CGRP、PAI-1、TXB2、6-keto-PGF1α的影响无统计学差异;复方菊明（5000mg.kg-）1能显著降低老年SHR的SBP（P〈0.01）、第8周起显著降低DBP（P〈0.01）,第4周明显降低MBP（P〈0.05）,第6周起显著降低MBP（P〈0.01）,降低血浆ET-1、TXB2、PAI-1含量（P〈0.01,P〈0.05,P〈0.05）,明显提高血清NO和血浆CGRP、6-keto-PGF1α（P〈0.05）;复方菊明与硝苯地平剂量减半（2500mg.kg-1＋3mg.kg-）1联合使用,仍能从第4周明显降低SBP（P〈0.05）,第6周起显著降低SBP（P〈0.01）,第4~6周明显降低DBP（P〈0.05）,第8周起显著降低DBP（P〈0.01）,第4周起显著降低MBP（P〈0.01）,降低血浆ET-1、TXB2、PAI-1含量（P〈0.01,P〈0.01,P〈0.05）,提高血清NO和血浆CGRP、6-keto-PGF1α（P〈0.01,P〈0.05,P〈0.05）。且联合用药组降低SBP、DBP和MBP,升高血浆CGRP的效果明显优于单独用药（P〈0.05）。[结论]复方菊明与硝苯地平联合用药起协同降压作用,较单独用药降压效果起效快,降低强度高于两药单用,且较单独用药更有效调节血管活性物质。

[Objective]To investigate the effect of compound Juming combined with nifedipine on blood pressure and vasoactive substances in aged spontaneously hypertensive rats（SHR）.[Method]The 14 months aged SHR rats were treated with drugs by ig.for 8 weeks.Systolic blood pressure（SBP）,diastolic pressure（DBP） and mean arterial pressure（MBP） of the rats were measured at 4,6 and 8 weeks.After the last treatment,blood samples were collected to detect plasma concentration of endothelin-1（ET-1）,calaitonin gene related peptide（CGRP）,nitric oxide（NO）,plasma plasminogen activator inhibitor-1（PAI-1）,blood clots grain B2（TXB2）,6-ketone-prostaglandin F1α（6-keto-PGF1α）.[Result]Compared with the model control group,nifedipine（6mg·kg-1）could significantly reduce SBP、MBP and plasma ET-1 level（P0.01）,from the 6th week MBP was decreased（P0.05）,increase serum NO level（P0.05）.The concentration of plasma CGRP,PAI-1,TXB2,6-keto-PGF1α were of no statistical difference.Compound Juming（5000mg·kg-1） could significantly reduce SBP（P0.01）,from the 8th week DBP was significantly decreased（P0.01）,the 4th week MBP was decreased（P0.05）,from the 6th week was significantly lower（P0.01）.The levels of plasma ET-1,TXB2 and PAI-1 were decreased（P0.01,P0.05,P0.05）.The levels of serum NO and plasma CGRP、6-keto-PGF1α were increased（P0.05）.Compound Juming combined with nifedipine in the half dose（2500mg·kg-1＋3mg·kg-1） from the 4th week could reduce SBP（P0.05）,from the 6th week could significantly reduce SBP（P0.01）,from the 4th to 6th week DBP was decreased（P0.05）,from the 8th week DBP was significantly lower（P0.01）,from the 4th week could significantly reduce MBP（P0.01）.The levels of plasma ET-1,TXB2 and PAI-1 were decreased（P0.01,P0.01,P0.05）,the levels of serum NO、plasma CGRP and 6-keto-PGF1α were increased（P0.01,P0.05,P0.05）.And combined medication group decreasing SBP,DBP and MBP,rising plasma CGRP was more than medication alone obviously（P0.05）.[Conclusion]When combined with Compound Juming,the antihypertensive effect was more fast and significant than the effect with nifedipine alone,which indicated these two drugs had synergistic antihypertensive effect.Also,compared with single administration,the combination treatment could regulate vasoactive substances more effectively.