摘要
目的:研究苯那普利对自发性高血压大鼠(SHR)细胞外信号调节激酶(ERK)和B型钠尿肽(BNP)的影响。方法:选择W istar Kyoto(WKY)大鼠作对照,将21只14周龄雄性SHR随机分成3组:未治疗组、肼苯哒嗪组和苯那普利组,每组7只。药物溶于载体(0.5%羧甲基纤维素钠)以灌胃法给予,肼苯哒嗪10 mg.kg-1.d-1,苯那普利10 mg.kg-1.d-1,SHR未治疗组及WKY组灌喂载体,共10周。以左心室重量与体重的比值反映心肌肥厚的程度;用袖带式尾动脉测压法测量大鼠尾动脉血压;分别用W estern b lotting方法和RT-PCR法半定量测定大鼠心肌中磷酸化ERK(p-ERK)的蛋白表达以及BNP mRNA的含量;酶联免疫吸附法检测大鼠血浆BNP水平。结果:(1)治疗后SHR苯那普利组和SHR肼苯哒嗪组血压相似,均显著低于SHR未治疗组(P<0.01)。(2)SHR苯那普利组心肌肥厚指数显著低于SHR肼苯哒嗪组和SHR未治疗组(P<0.01),与WKY组无显著差异(P>0.05);SHR肼苯哒嗪组和SHR未治疗组心肌肥厚指数无显著差异(P>0.05)。(3)SHR苯那普利组大鼠心肌p-ERK表达显著低于SHR肼苯哒嗪组和SHR未治疗组(P<0.05),与WKY组无显著差异(P>0.05)。SHR肼苯哒嗪组和SHR未治疗组大鼠心肌p-ERK表达无明显差异(P>0.05)。(4)SHR苯那普利组大鼠心肌BNP mRNA和血浆BNP水平显著低于SHR肼苯哒嗪组和SHR未治疗组(P<0.05),与WKY组无显著差异(P>0.05);SHR肼苯哒嗪组和SHR未治疗组大鼠心肌BNP mRNA和血浆BNP水平无明显差异(P>0.05)。结论:苯那普利能通过抑制ERK活性逆转心肌肥厚,伴随BNP水平下降;而降压效果相似的肼苯哒嗪不能抑制心肌肥厚,对p-ERK和BNP水平没有影响,提示BNP水平可以反映逆转心肌肥厚药物疗效。
AIM： To investigate the role of benazepril on extracellular signal -regulated kinase （ERK） activity and expression of B-type natriuretic peptide in spontaneously hypertension rat （SHR）. METHODS： Wistar Kyoto rats were used as control group. Twenty one 14 -week -age SHR were randomized into 3 groups, 7 rats each： benazepril group （ 10 mg · kg^- 1 · d ^-1 ） ; hydralazine group （ 10 mg · kg^- 1 . d^- 1 ） and sham group. In each group drugs or equal volume of vehicle （0. 5% carboxymethyl cellulose） were administered respectively for 10 weeks by gavage. The ratio of left ventricle weight to ＂body weight （LVW/BW） was measured to reflect myocardial hypertrophy. The caudal arterial pressure was measured by tail - cuff. Protein expression of p - ERK in myocardial tissue was detected by Western blotting, BNP mRNA in myocardial tissue was examined by RT - PCR, and protein expression of plasma BNP was detected by ELISA. RESULTS ： 1. Benazepril and hydralazine lowered the blood pressure after 10 weeks treatment （ P 〈 0. 01 ）. 2. The ratio of LVW/BW in SHR benazepril group was significantly lower than that in SHR hydralazine group and SHR sham group （ P 〈 0. 01 ）, and similar to that in WKY group （ P 〉 0. 05 ）. 3. The protein expression of p - ERK in myocardial tissue in SHR benazeprilgroup was significantly lower than that in SHR hydralazine group and SHR sham group （ P 〈 0. 01 ）, and similar to that in WKY. group （ P 〉 0. 05 ）. There was no significant difference of p - ERK expression between SHR hydralazine group and SHR sham group （ P 〉 0.05）. 4. The levels of plasma BNP and BNP mRNA in myocardial tissue in SHR benazepril group were significantly lower than that in SHR hydralazine group and SHR sham group （P 〈 0. 01 ）, and similar to that in WKY group （ P 〉 0. 05 ）. There was no significant difference of plasma BNP and BNP mRNA in myocardial tissue between SHR hydralazine group and SHR sham group （ p 〉 0. 05 ）. CONCLUSIONS： Benazep
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2006年第8期1524-1528,共5页
Chinese Journal of Pathophysiology
基金
杭州市医药卫生科技项目资助(No.2004BZ037)
杭州师范学院科研基金项目资助(No.2004XYQ06)
浙江省自然科学资金资助项目(No.M303874)
浙江省科技厅资助项目(No.021107057)
关键词
苯那普利
有丝分裂素激活蛋白激酶类
钠尿肽
B型
自发性高血压大鼠
心肌肥厚
Benazepril
Mitogen - activated protein kinases
Natriuretic peptide, B - type
Spontaneously hypertensive rats
Myocardial hypertrophy
