缺血性心功能不全家兔心肌ACE2/Ang-（1-9）/Ang-（1-7）轴的变化及培哚普利的治疗作用  

Changes of ACE2/Ang-（1-9）/Ang-（1-7） axis in ischemic cardiac dysfunction rabbits and the theraputic effects of Perindopril

作　　者：郝潇[1] 李树仁[1] 孟田田[1] 高青[1] 党懿[1] 荀丽颖[1] 苑可心[1] 张倩辉[1] 郝清卿[1] 齐晓勇[1] 

机构地区：[1]河北医科大学附属河北省人民医院心脏一科,河北省石家庄市050051

出　　处：《中国心血管病研究》2016年第7期658-662,670,共6页Chinese Journal of Cardiovascular Research

摘　　要：目的 探讨培哚普利对缺血性心功能不全家兔新型RAAS系统的影响.方法利用随机数字表法将30只家兔随机分为培哚普利组、心功能不全组和假手术组.培哚普利组及心功能不全组通过结扎冠状动脉前降支的方法制作缺血性心功能不全家兔模型,假手术组仅开胸不结扎冠状动脉.模型制作成功后培哚普利组给予培哚普利生理盐水溶液2 ml·kg^-1·d^-1灌胃（浓度为1 mg/ml）,心功能不全组及假手术组给予等量生理盐水灌胃.4周后心脏彩超测定心功能;Real-Time PCR检测血管紧张素转换酶2（ACE2）mRNA表达,ELISA检测家兔血清Ang-（1-9）和Ang-（1-7）水平.结果 与心功能不全组相比,培哚普利可显著改善心功能[（50.61±3.21）％比（46.44±1.66）％,P＜0.01];与假手术组相比,心功能不全家兔血清Ang-（1-9）[（3.86±0.49）ng/ml比（3.03±0.29） ng/ml,P＜0.01]和Ang-（1-7）[（3.82±0.59）ng/ml比（2.76±0.22）ng/ml,P＜0.01]水平均增高,心肌ACE2 mRNA表达显著增高（0.41±0.14比0.25±0.08,P＜0.01）;心功能不全家兔应用培哚普利后,血清Ang-（1-9）[（4.71±0.31）ng/ml比（3.86±0.49）ng/ml,P=0.001]和Ang-（1-7）[（4.42±0.50） ng/ml比（3.82±0.59）ng/ml,P=0.039]水平均增高,ACE2 mRNA表达增加（0.98±0.14比0.41±0.14,P＜0.01）.相关性分析显示,缺血性心功能不全家兔心功能与心肌ACE2 mRNA表达呈正性相关关系,相关系数为0.770（P=0.003）.结论心功能不全家兔RAAS系统激活的同时还伴有新型RAAS系统的抑制,而培哚普利可以通过ACE2/Ang-（1-9）/Ang-（1-7）这一新型RAAS通路发挥心脏保护性作用.Objective To investigate effects of Perindopril on ACE2/Ang-（1-9）/Ang-（1-7） axis in ischemic cardiac dysfunction rabbits. Methods 30 male rabbits were selected. The rabbits were randomly divided into 3 groups（n=10）： Perindopril group, cardiac dysfunction group and control group. The left anterior descending coronary arterys of the rabbits were ligatured for model preparation. In the Perindopril group, rabbits were treated with Perindopril split normal saline solution 2 mkg^-1·d^-1（1 mg/ml）. In cardiac dysfunction group and control group, rabbits were treated with normal saline solution 2 mlkg^-1·d^-1（0.33 mg/ml）. 4 weeks after treatment, cardiac function was measured via echocardiography, angiotensin-converting enzyme 2 mRNA expression was analyzed by real-time PCR, serum Ang-（1-9） and Ang-（1-7） level ware detected by enzyme linked immunosorbent assay. Results Compared with control group, the cardiac function of the other two groups were significantly reduced（50.61±3.21 vs 46.44±1.66, P〈0.001）; but the serum Ang-（1-9）（3.86±0.49 vs 3.03±0.29, P〈0.01） and Ang-（1-7）（3.82±0.59 vs 2.76±0.22, P〈0.01） level and the ACE2（0.41±0.14 vs 0.25±0.08, P〈0.01） mRNA expression of the other two groups were significantly improved. Compared with cardiac dysfunction group, Perindopril group got significant improvement in ACE2（0.41±0.14 vs 0.25±0.08, P〈0.01） mRNA expression and the serum level of Ang-（1-9）（4.71±0.31 vs 3.86±0.49, P=0.001） and Ang-（1-7）（3.82±0.59 vs 2.76±0.22, P〈0.01）. Correlation analysis revealed that the improvement of the cardiac function was associated with ACE2 mRNA expression（R=0.770, P=0.003）. Conclusion Accompanied by RAAS activated in ischemic cardiac dysfunction rabbits, the ACE2/Ang-（1-9）/Ang-（1-7） was also activated. Perindopril can improve cardiac function via ACE2/Ang-（1-9）/Ang-（1-7） axis.

关 键 词：缺血性心功能不全 肾素-血管紧张素-醛固酮系统 血管紧张素转换酶2 血管紧张素转换酶抑制剂 

分 类 号：Q95-33[生物学—动物学] R542.2[医药卫生—心血管疾病]