福辛普利对自发性高血压大鼠氧化应激水平及血管功能的影响

Effects of Fosinopril on Oxidative Stress and Vascular Function in Experimental Rats With Spontaneous Hypertension

目的:探讨福辛普利对自发性高血压大鼠氧化应激水平及血管功能的影响。方法:大鼠分3组:正常对照组(n=15)、自发性高血压组(高血压组,n=15)、自发性高血压福辛普利治疗组(治疗组,n=15)。治疗组每日予灌胃福辛普利[10 mg/(kg·d)],高血压组则予灌胃等体积生理盐水,每周测量尾动脉收缩压(SBP)。7周后检测血浆氧化物歧化酶(SOD)、血清活性氧(ROS)、丙二醛(MDA)、一氧化氮代谢产物(NO2-/NO3-)水平;并取胸主动脉,检测其对乙酰胆碱(Ach)/硝普钠(SNP)的舒张率。结果:自第1周末开始至结束,治疗组的SBP较高血压组均显著下降(P<0.05)。7周后,高血压组的血浆SOD活性较正常对照组明显下降(P<0.05),而血清MDA及ROS水平则显著上升(P<0.05);但经福辛普利治疗后,治疗组大鼠的血浆SOD活性较高血压组有所上升(P=0.010),且MDA、ROS水平下降(MDA:P=0.021;ROS:P=0.009),差异均有统计学意义。高血压组NO2-/NO3-含量较正常对照组显著下降(P<0.001),高血压组和治疗组对Ach/SNP诱导的血管舒张率均较正常对照组显著下降(P<0.05)。治疗组血清NO2-/NO3-含量显著高于高血压组(P<0.001);对比高血压组,治疗组对Ach(P<0.001)诱导的血管舒张率有明显上升。结论:福辛普利通过抗氧化应激改善血管舒张功能,可能是其发挥降压作用的机制之一。

Objective： To explore the effects of fosinopril on oxidative stress and vascular function in experimental rats with spontaneous hypertension. Methods： The rats were divided into 3 groups： Control group, with normal healthy rats （n=15）, Spontaneous hypertension （SH） group （n=15）, SH rats received intragastric administration of normal saline and Treatment group （n=15）, SH rats received intragastric administration of fosinopril 10mg/（kg·d）. All animals were treated for 7 weeks. Caudal artery systolic blood pressure （SBP） was measured at each week. blood levels of superoxide dismutase （SOD）, reactive oxygen species （ROS）, malonaldehyde （MDA） and NO2-/NO3- were determined in different groups respectively after 7 weeks. Moreover, thoracic aorta was taken to examine its diastolic reactive rate by acetylcholine （Ach）/sodium nitroprusside （SNP） induction. Results： From the 1^st week until the end of experiment, compared with SH group, Treatment group had decreased SBP,P〈0.05. With 7 weeks treatment, compared with Control group, SH group had decreased SOD activity, while increased protein levels of MDA and ROS, allP〈0.05; compared with SH group, Treatment group showed elevated SOD activity （P=0.010）, while reduced protein levels of MDA （P=0.021） and ROS （P=0.009）. Compared with Control group, SH group had the lower content of NO2-/NO3-（P〈0.001）; both SH group and Treatment group had decreased diastolic rates by Ach/SNP induction,P〈0.05. Compared with SH group, Treatment group presented the higher content of NO2-/NO3- and higher diastolic rate by Ach induction, allP〈0.001.＆amp;nbsp;Conclusion： Fosinopril could improve vascular diastolic function via anti-oxidative stress in experimental SH rats, which might be one of its anti-hypertensive mechanisms.