几种肾素-血管紧张素系统抑制剂对正常大鼠血浆细胞因子和心肌eNOS、Caspase-3蛋白表达的影响

目的观察几种血管紧张素转换酶抑制剂（ACEI）培哚普利、雷米普利、福辛普利、卡托普利及血管紧张素受体拮抗剂（ARB）替米沙坦对正常大鼠用药后血浆细胞因子VEGF、eNOS、TNF-α、vWF、NO水平及心肌eNOS及Caspase-3蛋白表达的影响。方法48只SD大鼠随机分为6组,每组8只,1组空白对照,余5组药物干预,给药组每日灌胃,分别给予培哚普利（1.33mg/kg）、雷米普利（1.67 mg/kg）、福辛普利（6.67 mg/kg）、卡托普利（25 mg/kg）或替米沙坦（13.33 mg/kg）,对照组给予生理盐水,2周后取外周血应用ELISA法检测血浆VEGF、eNOS、TNF-α、vWF的含量,硝酸还原酶法检测血浆NO含量,免疫组化方法观察心肌eNOS表达,免疫荧光方法观察心肌vWF表达,Western-blot分析心肌eNOS及Caspase-3的蛋白表达。结果服药2周后,血浆TNF-α、vWF数值明显下降,较对照组差异显著（P〈0.05）,药物组间对比未见明显差异,VEGF有所升高但未达到统计意义（P〉0.05）, eNOS水平亦有所升高,与对照组比较雷米普利组、卡托普利组及替米沙坦组差异显著（P〈0.05）,各药物组间差异无显著性。血浆NO含量有升高趋势,但未达到统计学差异,各组均（P〉0.05）。免疫组化方法观察心肌eNOS在小血管内皮及心肌细胞胞膜及胞浆表达。免疫荧光亦可观察到vWF在心肌血管内皮的表达。Western-blot分析药物组心肌eNOS蛋白表达增加,与对照组相比,卡托普利组、替米沙坦组差异达到显著性（P〈0.05）,Caspase-3蛋白有所减低,与对照组相比,福辛普利组、替米沙坦组差异达到显著性（P〈0.05）。结论正常大鼠灌胃给予ACEI或ARB类药物也可降低血浆TNF-α、vWF水平并提高eNOS的含量,增加心肌组织eNOS及降低Caspase-3蛋白表达,各治疗组间作用无显著差异。

Effects of several anti-renin-angiotensin-system agents on plasma cytokines and cadiocyte protein expression of eNOS and Caspase-3 in healthy rat

Objective To investigate the effects of different kinds of angiotensin-converting enzyme inhibitor（ACEI）, including perindopril, ramipril , fosinopril, captopril and angiotensin receptor antagonist （ARB） telmisartan on plasma cytokines and cadiocyte protein expression of eNOS and Caspase-3 in healthy rat. Methods 48 SD rats were divided into one control group and five treatment groups according to different kinds of ACEI or ARB, including 1.33 mg/（kg, d） perindopril, 1.67mg/（kg. d） ramipril, 6.67 mg/（kg. d） fosinopril, 25 mg/（kg, d）captopril and 13.33 mg/（kg, d） telmisartan respectively for 2 weeks. Plasma VEGF,eNOS,TNF-α,vWF concentrations were detected by ELISA. The plasma level of NO was measured by Griess method. Western-blot were used to detect the changes of cadiocyte protein expression of eNOS and Caspase-3 . Result The plasma concentrations of TNF-α,vWF were lower in all treatment groups than those in control group（ all P 〈 0.05 ）, and the plasma VEGF concentration was slightly increased in all treatment groups than that in control group（P 〉0.05）. Plasma eNOS concentration of ramipril group, captopril group and telmisartan group were all significantly increased compared with the control group （P 〈 0.05 ）. The plasma concentration of NO wasn＇ t significantly increased in all treatment groups than that in control group （ P 〉 0.05 ）. The eNOS levels of cadiocyte protein expression in all treatment groups were higher than that in control group, and telmisartan group and captopril group were more notable （ P 〈 0.05 ）. The levels of caspase- 3 in all treatment groups were decreased than that in control group, and the telmisartan, fosinopril groups were more notable （P 〈0.05）. Conclusions ACEI and ARB can increase the plasma level of eNOS, and decrease TNF-α,vWF concentrations in healthy rat. Meanwhile ACEI and ARB increase cadiocyte protein expression of eNOS and decrease Caspase-3 expression in healthy rat. The difference among all treatment agents was not significant.