新型磷酸二酯酶5抑制剂CPD1对异丙肾上腺素诱导心肌肥厚大鼠心脏的保护作用  

The protective effect of a novel phosphodiesterase type 5 inhibitor, CPD1, on isoprenaline-induced cardiac hypertrophy in rats

作　　者：刘晓晴 杨建钦 王栩林 李斌 封文斌 高洁 赵子建 穆云萍 李芳红 LIU Xiao-qing;YANG Jian-qin;WANG Xu-lin;LI Bin;FENG Wen-bin;GAO Jie;ZHAO Zi-jian;MU Yun-ping;LI Fang-hong(School of Biomedical and Pharmaceutical Sciences,Guangdong University of Technology,Guangzhou 510006,China;The Second School of Clinical Medicine,Southern Medical University,Guangdong Provincial People's Hospital,Guangzhou 510080,China)

机构地区：[1]广东工业大学生物医药学院,广东广州510006 [2]南方医科大学第二临床医学院,广东省人民医院,广东广州510080

出　　处：《中国药理学通报》2022年第9期1388-1394,共7页Chinese Pharmacological Bulletin

基　　金：国家重点研发计划项目(No 2018YFA0800603);广东省重点领域研发计划项目(No 2019B020201015);广东省“珠江人才计划”项目(No 2016ZT06Y432);广东省自然科学基金面上项目(No 2020A1515011302);心血管病离子通道信号调控福建省高校重点实验室开放课题基金项目(No FMUISCD-201801)。

摘　　要：目的 观察新型磷酸二酯酶5(phosphodiesterase 5,PDE 5)抑制剂CPD1对心肌肥厚大鼠心脏的保护作用。方法 利用异丙肾上腺素(isoprenaline)持续腹腔注射(5 mg·kg^(-1)·d^(-1)),制备心肌肥厚大鼠模型,造模当天分别给予CPD1(5 mg·kg^(-1)·d^(-1))、传统PDE5抑制剂西地那非(20 mg·kg^(-1)·d^(-1))、阳性对照药依那普利(10 mg·kg^(-1)·d^(-1))灌胃治疗,持续7 d。通过血流动力学检测、心脏组织病理学分析及分子生物学技术,观察CPD1对异丙肾上腺素诱导的心肌肥厚大鼠左心功能的保护作用。结果 成功制备心肌肥厚大鼠模型;CPD1治疗明显恢复左心室收缩压,改善左心收缩和舒张功能,明显降低心脏质量指数和左心室质量指数,减小心肌细胞的横截面积,降低左心组织中肥大标志基因心房钠尿肽和脑钠肽的含量。与西地那非和依那普利治疗组相比,CPD1对左心功能的改善作用更显著。结论新型PDE5抑制剂CPD1对异丙肾上腺素诱导的心肌肥厚有显著的保护作用,能够明显改善模型大鼠心脏的收缩和舒张功能。Aim To evaluate the protective effect of CPD1, a novel phosphodiesterase 5 inhibitor, on isoprenaline-induced cardiac hypertrophy in rats. Methods Isoprenaline-induced cardiac hypertrophy was generated by intraperitoneal injection of isoprenaline(5 mg·kg^(-1)·d^(-1)) in rats. After isoprenaline injection the rats were treated with CPD1(5 mg·kg^(-1)·d^(-1)), sildenafil(20 mg·kg^(-1)·d^(-1)), or enalapril(10 mg·kg^(-1)·d^(-1)), respectively, for seven days. Results The protective effect of CPD1 was examined using hemodynamic detection, pathological analysis of cardiac and molecular biology techniques in the isoprenaline-treated rats. The results showed that isoprenaline treated rats exhibited profound cardiac hypertrophy one week after injection. In contrast, gavage administration of CPD1 led to significant restoration of the left ventricular systolic pressure, improved left ventricular systolic and diastolic functions, and reduced cardiac hypertrophy index as well as left ventricular relative weight. Furthermore, cross section area of cardiomyocytes, atrial natriuretic peptide and brain natriuretic peptide mRNA expression significantly decreased in the CPD1 group compared to the cardiac hypertrophic model group. Of particularly note, CPD1 could restore cardiac function when compared to the sildenafil and enalapril treated groups. Conclusions The novel PDE inhibitor, CPD1, displays strong protective effects against isoprenaline induced cardiac hypertrophy, and CPD1 could improve the cardiac functions of hypertrophic heart.

关 键 词：磷酸二酯酶5抑制剂 CPD1 心肌肥厚 异丙肾上腺素 心肌肥大因子 心功能 

分 类 号：R-332[医药卫生] R322.11R331.31R542.2R977.3