葛根素影响自发性高血压大鼠血压的机制

目的：研究葛根素影响自发性高血压大鼠血压的分子机制。方法：12只成年自发性高血压大鼠（SHR）随机分为给药组和对照组,给药组灌胃葛根素（36mg.kg.d-1）,对照组灌胃等量去离子水。每周测血压1次,4周后处死动物,分别检测肾脏、肝脏和血管中内皮素-1（ET-1）、一氧化氮合酶（NOS）、细胞色素P450 4A1（CYP4A1）和血管紧张素Ⅱ-1型受体（AT-1）mRNA和蛋白质的表达量,检测血浆中血管紧张素Ⅱ和醛固酮含量。结果：葛根素给药4周后,可显著上调肾脏、肝脏和血管中eNOS mR-NA的表达,下调肝脏中ET-1的蛋白含量;显著上调肾脏和血管中CYP4A1 mRNA和蛋白水平,以及AT-1 mRNA水平。结论：葛根素可能主要通过上调eNOS和下调ET-1的表达,降低SHR的血压;通过激活肾素-血管紧张素-醛固酮系统（RAAS）和花生四烯酸羟化代谢途径,拮抗降压作用。

Effect of Puerarin on the Blood Pressure of Spontaneously Hypertensive Rat

Objective： To investigate the molecular mechanism of the effect of puerarin on the blood pressure of spontaneously hypertensive rats（SHR）.Methods： 12 SHRs group were randomly divided into control and puerarin treatment group.Rats of puerarin administered 36mg/kg puerarin once a day for 4 weeks,and rats of control group were orally dosed equal amount of physiological saline.All animals were sacrificed at the end of 4th weeks.The content of AngⅡ and ALD in plasma were determined by radioimmunoassay.The mRNA levels of ET-1,eNOS,CYP4A1 and AT-1 in kidney,liver and blood vessel were determined by real-time RT-PCR.The protein levels of CYP4A1 in kidney,liver and blood vessel were determined by Western Blotting analysis.Results： Compared with the control group,puerarin can effectively down regulate the protein level of ET-1 in liver,up regulate the mRNA level of eNOS in kidney,liver and blood vessel,up regulate the mRNA and protein levels of CYP4A1 in kidney and blood vessel,up regulate the mRNA levels of AT-1 in kidney and blood vessel.Conclusion： The results indicated that the up-regulation of eNOS and down-regulation of ET-1 in mRNA and/or protein levels may be the important antihypertensive reason of puerarin for SHRs,and the activation of RAAS and hydroxylation metabolism of arachidonic acid induced by puerarin may be the important reason of SHRs blood pressure up-regulation.