β_1肾上腺素能受体反义寡核苷酸对自发性高血压大鼠心肌MMP-2蛋白表达的影响  

Effects of Antisense Inhibition of β_1-Adrenergic Receptor mRNA on protein Expression of MMP-2 in heart of Spontaneously Hypertensive Rats

作　　者：王金波[1] 曹树军[1] 王立中[1] 谢刚[1] 

机构地区：[1]北京市大兴区人民医院心内科,北京102600

出　　处：《中国医药导刊》2006年第3期210-213,共4页Chinese Journal of Medicinal Guide

摘　　要：目的:观察中以阳离子脂质体载体介导的β1肾上腺素能受体反义寡核苷酸对自发性高血压大鼠左室心肌中基质金属蛋白酶-2(MMP-2)蛋白表达其细胞外间质的影响。方法:20只雄性19周龄SHR随机分为阳性对照组(n=6),反义(ASODN)治疗组(n=7,尾静脉β1-AS-ODN 1．0mg·kg-1·20d-1,共3次),反向(INODN)治疗组(n=7),尾静脉注射β1-IN-ODN 1．0mg·kg-1·20d-1,共3次),另选同龄雄性Wistar Kyoto(WKY)大鼠为正常对照(n=6)。常规方法测定尾动脉收缩压及左心室重量指数(LVI),Van Gieson染色法检测左室胶原容积分数(CVF),免疫组化法检测左室心肌MMP-2蛋白表达,RT-PCR法检测左室心肌β1肾上腺素能受体mRNA表达。结果:(1)与WKY组大鼠相比较,28周龄SHR存在高血压,心肌肥大及纤维化;(2)与SHR组比较,β1-AS-ODN治疗组大鼠左室心肌β1-AR mRNA表达及MMP-2蛋白表达减少,血压及LVI、CVF降低。结论:β1-AS-ODN在转录水平抑制SHRβ1-AR的表达,在持久而有效降压的同时,可能通过减少心肌中MMP-2蛋白表达逆转左室肥大、纤维化。Objective： To investigate whether antisense oligonueleotides against rat β1- adrenergie receptor（ β1 - AR） mRNA （β1- AS - ODN） delivered in cationic hposomes can reverse cardiac fibrosis through reducing myocardial matrix metalloproteinase - 2（MMP - 2） protein expression of spontaneously hypertensive rats （SHRs） .Methods： This study was performed in 20 19 - week - old male SHRs and 6 age - matched male Wistar Kyoto Rats（WKY）. Two groups of SHRs were treated via tail vein injection with β1- AS - ODN（n = 7, 1.0mg · kg^-1· 20d^-1 ） or inverted oligonucleotides against rat β1 - AR mRNA（β1 - IN - ODN） （n = 7, 1.0 mg· kg^- 1· 20d^-1 ） for 3 times. 6 untreated SHRs and 6 WKY rats served as positive and normal controls respectively. Blood pressure（BP）, left ventficular index（LVI） were measured; Left ventricular collagen volume fraction（CVF） was examined by Van Gieson method; The expression of MMP - 2 were examined by immunohistochemistry; The expression of β1 - AR mRNA in left ventricle was measured with RT-PCR.Results： （1） Compared with WKY rats, SHRs exhibited significantly increased BP, LVI, CVF; （2） With the significantly decreased expression of left ventricular β1 - AR mRNA and MMP - 2, β1 - AS - ODN treated SHRs exhibited significantly decreased BP, LVI and CVF. Conclusion： Through antisense inhibition of β1 - AR mRNA at transcriptional level in SHR, treatment with β1 - AS - ODN can reverse left ventricular fibrosis possiblely through reducing myocardial MMP - 2 protein expression.

关 键 词：反义寡核苷酸 基因治疗 Β1肾上腺素能受体 自发性高血压大鼠 基质金属蛋白酶 

分 类 号：R544.1[医药卫生—心血管疾病]