Val-Glu-Pro对原发性高血压大鼠的体内降压作用

In vivo Antihypertensive Effect of Val-Glu-Pro in Spontaneously Hypertensive Rats

Val-Glu-Pro(VEP)是从钝顶螺旋藻(Spirulina platensis)中发现的一种血管紧张素转化酶(ACE)抑制肽.以原发性高血压大鼠(SHR)为模型,检测单次口服和一周间口服VEP的降压效果,并通过Real-timePCR和酶联免疫吸附法(ELISA)探索其对肾素-血管紧张素系统(RAS)主要成分在SHR大鼠肾脏和血清中的表达调控作用.结果表明:口服VEP的最低有效降压剂量为5mg/kg,加大剂量后表现出剂量效应,最低加权收缩压(WSBP)出现在口服后6h,最低加权舒张压(WDBP)出现在口服后4 h.在一周间口服试验中,10 mg/kg VEP处理组的WSBP在第5日显著低于负对照组.此外,口服VEP显著下调了SHR大鼠肾脏中肾素(renin)、ACE、血管紧张素Ⅱ(AngⅡ)类型1受体(AT1)的mRNA表达,并上调AngⅡ类型2受体(AT2)的mRNA表达,说明VEP的降压效果可能与对RAS系统的抑制作用相关,在高血压的预防和治疗中具有潜在的应用前景.

Val-Glu-Pro（VEP） is an angiotensin Ⅰ-converting enzyme（ACE） inhibitory peptide derived from Spirulina platensis.The antihypertensive effect of VEP in spontaneously hypertensive rats（SHRs） was investigated in 24 h after one single dose and in one-week with one single dose per day.The expression regulation of VEP on major components of the renin-angiotensin system（RAS） in the kidney and serum of the SHRs was also explored with Real-Time PCR and enzyme-linked immunosorbent assay（ELISA）.The results indicated that the least effective dose of VEP was 5 mg/kg and it exhibited a dose-dependent manner with increased dosages.The lowest weighted systolic blood pressure（WSBP） and weighted diastolic blood pressure（WDBP） occurred in 6 h and 4 h after administration,respectively.During the one-week experiment course,the WSBP of the VEP-treated group（10 mg/kg） was significantly lower than that of the negative control group from the 5th day.Furthermore,the VEP treatment significantly down-regulated the mRNA expression of renin,ACE,and the angiotensinⅡ（AngⅡ） type 1（AT1） receptor,and up-regulated the mRNA expression of the AngⅡ type 2（AT2） receptor in the kidney of the SHRs,suggesting that the antihypertensive effect of VEP might be related to its inhibition on the RAS and that it might be of great prospects in prevention and treatment of hypertension.