合成二肽ACE抑制活性及抗高血压初步研究

A preliminary study of inhibitory activities on angiotensin I-converting enzyme and antihypertensive effects of synthetic dipeptide

目的:对合成二肽的ACE抑制活性进行系统地筛选,寻找具有高ACE抑制活性的二肽并研究其在动物体内的降血压作用。方法:利用可见光分光光度法对35种合成二肽的ACE抑制活性进行测定,并对具有高ACE抑制活性的二肽进一步测定其IC50值。选取ACE抑制效果最佳的二肽进行原发性高血压大鼠(SHR)降血压实验。实验采用灌胃方法分别以1、10、25、50、100 mg/kg的剂量溶于1 m L生理盐水进行给药,分别于给药后2 h和4 h测量大鼠血压变化。结果:研究发现大部分二肽都具有一定程度的ACE抑制活性,其中以氨基酸序列为半胱氨酸-丙氨酸(Cys-Ala,CA)和半胱氨酸-组氨酸(CysHis,CH)的二肽ACE抑制活性最高,其ACE抑制率分别达到84.38%和70.79%。经测定CA和CH的IC50值分别为23.22μmol/L和61.17μmol/L。SHR大鼠降血压实验表明CA在体内的降压效果显著。给药后4 h CA降压效果优于给药后2 h,给药后2 h CA降压效果与给药剂量呈较好的正相关性(R2>0.8)。结论:体外ACE抑制率测定及SHR大鼠降血压实验发现合成二肽CA具有较高的ACE抑制活性和较好的体内降血压效果,提示CA可以作为降血压保健食品的添加成分,值得进一步研究。

Objective：The purpose of this work was to study the inhibitory activities on angiotensin I-converting enzyme（ACE） and the antihypertensive effects of synthetic dipeptides. Methods：The inhibitory activities on ACE of35 synthetic dipeptides were screened by using ultraviolet and visible spectrophotometry. The IC50 of dipeptides with high inhibitory activity was also measured. The antihypertensive effects of dipeptides were subsequently studied in spontaneously hypertensive rats（SHR） at 2 h and 4 h after oral administration diluted in 1 m L normal saline according to the dosages of 1,10,25,50,100 mg/kg,respectively. Results：With the exception of a few dipeptides,most of dipeptides showed ACE inhibitory activities. Among them,Cys-Ala（CA） and Cys-His（CH）were dipeptides with the highest ACE inhibitory activities,of which the ACE inhibition rates were 84.38% and 70.79%respectively. The dose response data showed the IC50 values of CA and CH were 23.22 μmol/L and 61.17 μmol/L respectively. The antihypertensive effects of CA in spontaneously hypertensive rats（SHR） were further studied. The data showed obvious antihypertensive effect of CA in SHR. The results also revealed that the antihypertensive effects after 2 h of administration was positively correlated with doses of oral administration（R20.8）,and the overall antihypertensive effects after 4 h of administration were higher than that after 2 h of administration. Conclusion：Based on the results of determination on in vitro ACE inhibitory activities and in vivo experiments,CA was the dipeptide with high ACE inhibition rate and strong antihypertensive effect,which suggested CA could be used as functional food ingredients with potential therapeutic benefit in the prevention and treatment of hypertension.