苯那普利对高血压大鼠细胞外信号调节激酶和B型钠尿肽的影响  

Role of benaeepfi on extracellular signal-regulated kinases activity and expression of B-type natriuretic peptide in spontaneously hypertensive rats

作　　者：王战坤[1] 黄朝阳[1] 

机构地区：[1]浙江大学医学院附属第一医院高级病房,310003

出　　处：《中国老年保健医学》2006年第4期30-34,共5页Chinese Journal of Geriatric Care

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Wistar Kyoto(WKY)大鼠作对照,将21只14周龄雄性SHR随机分成3组:SHR未治疗组、SHR肼苯哒嗪组和SHR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10mg·kg-1·d-1,苯那普利10mg·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Western blot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)。②SHR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)。③SHR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)。④SHR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BNPmRNA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 benaeepil on extracellular signal-regulated kinase (ERK) activity and expression of B-type natriuretic peptide in spontaneously hypertensive rat (SHR). Method We chose Wistar Kynto rats as control group. Twenty one 14-week-age SHR were randomizedly divided into 3 groups, 7 rats each: benaeepil 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 (0.5WTB3% 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 blot, BNP mRNA in myocardial tissue was examined by RT-PCR, and protein expression of plasma BNP was detected by ELISA. Result 1. Benaeepil and hydralazine lowered the blood pressure after l0 weeks treatment (P<0.01).2. The ratio of LVW/BW in SHR benaeepil 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 benaeepil group was significantly lower than that in SI-IR 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 level of plasma BNP and BNP mRNA in myocardial tissue in SHR benaeepil group were significantly lower than that in SHR hydralazine group and SI-IR sham group (P<0.01) , and similar to that in WKY group (P>0.05) . There were no significant difference of plasma BNP and BNP mRNA in myocardial tissue between SHR hydralazine group and SHR sham group(P>0.05). Conclusion Benaeepil could inhibit ERK activation so as to result in regression of myocardial hypertrophy, being accompanied by the reduction of BNP level. However, in spit

关 键 词：血管紧张素转化酶抑制剂 细胞外调节激酶 B型钠尿肽 心肌肥厚 

分 类 号：R544.1[医药卫生—心血管疾病]