| 引用本文: | 黄芸,张梅珍,邢晓为,陆瑶,刘心瑶,李莹,黄志军,袁洪.自发性高血压大鼠心肌β1肾上腺受体过表达对美托洛尔降压疗效的影响[J].中国现代应用药学,2015,32(11):1289-1293. |
| HUANG Yun,ZHANG Meizhen,XING Xiaowei,LU Yao,LIU Xinyao,LI Ying,HUANG Zhijun,YUAN Hong.Antihypertensive Effects of Metoprolol on Spontaneously Hypertensive Rats of Cardiac β1-AR Overexpression[J].Chin J Mod Appl Pharm(中国现代应用药学),2015,32(11):1289-1293. |
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| 自发性高血压大鼠心肌β1肾上腺受体过表达对美托洛尔降压疗效的影响 |
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黄芸1,2, 张梅珍1,2, 邢晓为2, 陆瑶2, 刘心瑶2, 李莹2, 黄志军2, 袁洪2
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1.中南大学药学院，长沙 410013;2.中南大学湘雅三医院临床药理中心，长沙 410013
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| 摘要: |
| 目的 探讨自发性高血压大鼠(spontaneously hypertensive rats，SHR)心肌β1肾上腺受体(β1-AR)表达上调对美托洛尔降压疗效的影响。方法 24只SHR随机分为AAV/Adrb1组、假手术组、AAV/Adrb1+美托洛尔组(AAV/Adrb1+Met组)和假手术+美托洛尔组(Sham+Met组)，每组6只。携带β1-AR质粒的AAV载体病毒(AAV/Adrb1，2×1012 vg·mL-1)经腹心包腔内注射术转染SHR。病毒干预4周后，应用RT-PCR、Western blot法及免疫组化法检测AAV/Adrbl组和假手术组大鼠心肌β1-AR表达，观察AAV/Adrb1对SHR心肌β1-AR表达的影响；分别给予AAV/Adrb1+Met和Sham+Met组美托洛尔(25 mg·kg-1·d-1)灌胃处理，持续4周监测SHR血压，观察心肌β1-AR表达上调对美托洛尔降压疗效的影响。结果 与假手术组相比，AAV/Adrbl组心肌β1-AR mRNA和蛋白表达水平显著升高(P<0.05)。美托洛尔干预时，AAV/Adrb1+Met组大鼠收缩压降低幅度显著高于Sham+Met组(P<0.05)。结论 SHR心肌β1-AR过表达提高美托洛尔的降压疗效，心肌β1-AR表达水平可能是影响美托洛尔疗效个体差异的因素之一。 |
| 关键词: β1肾上腺受体 心肌 过表达 美托洛尔 自发性高血压大鼠 |
| DOI： |
| 分类号:R544.1 |
| 基金项目:国家自然科学基金(81470535)；十二五国家科技支撑计划课题(2012BAI37B05)；中南大学创新课题(2014zzts089) |
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| Antihypertensive Effects of Metoprolol on Spontaneously Hypertensive Rats of Cardiac β1-AR Overexpression |
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HUANG Yun1,2, ZHANG Meizhen1,2, XING Xiaowei2, LU Yao2, LIU Xinyao2, LI Ying2, HUANG Zhijun2, YUAN Hong2
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1.School of Pharmacy, Central South University, Changsha 410013, China;2.Center for Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha 410013, China
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| Abstract: |
| OBJECTIVE To investigate the antihypertensive effects of metoprolol on spontaneously hypertensive rats (SHR) of cardiac β1 adrenergic receptors (β1-AR) overexpression. METHODS Twenty-four twenty-week-old male SHR were divided into the AAV/Adrb1 group, sham group, the AAV/Adrb1 + metoprolol group (AAV/Adrb1+Met) and sham+metoprolol group (Sham+Met) (n=6). Adeno-associated virus vector expressing Adrb1 (AAV/Adrb1, 2×1012 vg·mL-1) was utilized to transfect SHR myocardium by the pericardial cavity. RT-PCR, Western blot and immunohistochemistry were performed to measure β1-AR expression in myocardium of AAV/Adrb1 group and sham group to investigate the effect of AAV/Adrb1 on SHR of cardiac β1-AR level after 4 weeks. And metoprolol (25 mg·kg-1·d-1 by gavage) intervention for 4 weeks, blood pressure of AAV/Adrb1+Met and Sham+Met groups were monitored weekly to study antihypertensive effect of metoprolol on SHR of cardiac β1-AR overespression. RESULTS β1-AR expression in myocardium of AAV/Adrb1 group was significantly upregulated compared with the sham group (P<0.05). While metoprolol intervention, the SBP drop pressure amplitude of the AAV/Adrb1+Met was significantly higher compared with the Sham+Met(P<0.05). CONCLUSION It has an better antihypertensive effect on SHR of cardiac β1-AR overexpression for metoprolol, and cardiac β1-AR expression may be one of the factors that affect metoprolol individual differences. |
| Key words: β1 adrenergic receptor cardiac overexpression metoprolol spontaneously hypertensive rat |
