脉君安片的降压抵抗机制研究

Study on the Antihypertensive Mechanisms of Maijunan Tablets

目的:研究脉君安片对自发性高血压大鼠(SHR)细胞色素P450羟化酶和肾素-血管紧张素-醛固酮系统(RAAS)的影响,探讨其降压抵抗机制。方法:12只成年SHR随机分为给药组和对照组,给药组灌胃模拟脉君安片(氢氯噻嗪10mg.kg-1.d-1,葛根素36mg.kg-1.d-1,钩藤总碱122mg.kg-1.d-1),对照组灌胃等量去离子水。每周测血压1次,4wk后处死动物。用放射免疫法检测血浆中血管紧张素Ⅱ和醛固酮含量,实时荧光定量PCR测定组织中细胞色素P450 4A1(CYP4A1)和血管紧张素Ⅱ1型受体(AT1)mRNA的表达,western blot法测定组织中细胞色素P450 4A1(CYP4A1)蛋白的表达量。结果:与对照组相比,用药4wk时给药组不仅降压效果显著,而且显著上调CYP4A1 mRNA和蛋白水平、血管紧张素Ⅱ1型受体(AT1)mRNA水平、血浆中血管紧张素Ⅱ和醛固酮的含量。结论:脉君安片在降低血压的同时,激活了肾素-血管紧张素-醛固酮系统和花生四烯酸羟化代谢途径,对降压产生了抵抗作用。

Objective： To investigate the effects of Maijunan Tablets on renin-angiotensin-aldosterone system（RAAS） and cytochrome P4A1 activity for arachidonic acid metabolism,and explore the depressurization counteraction mechanism of Maijunan Tablets.Methods： 12 spontaneous hypertensive rats（SHR） were divided randomly into normal control group and drug administration group.Rats in drug administration group were orally dosed Maijunan Tablets（hydrochlorothiazide 10 mg/kg/d,puerarin 36 mg/kg/d and total alkaloid of rhynchophylla 122 mg/kg/d） once a day for 4 weeks,and rats in control group were orally dosed equal amount of physiological saline.All animals were sacrificed at 4 weeks..The concentration of AngⅡ and ALD in plasma were determined by radioimmunoassay.The mRNA expression amounts of CYP4A1 and AT1 in major organs were determined by Real-time quantitative PCR.The contents of CYP4A1 in major organs were determined by western blot.Results： Compared with the control group,Maijunan Tablets can effectively reduce blood pressure of SHRs,up regulate the expression of AT1 at mRNA levels and CYP4A1 at mRNA and protein levels,up regulate AngⅡand ALD.Conclusion： Maijunan Tablets can activiae RAAS and the hydroxylation metabolism of arachidonic acid,to induce depressurization counteraction of SHR.