ATP敏感性钾通道开放剂埃他卡林逆转心室重构及其内皮细胞机制  

Effects of ATP-sensitive potassium channel opener iptakalim against ventricular remodeling and its mechanisms of endothelial protection

作　　者：钟明利[1,2] 汪汇[3] 周红敏[2] 张雁芳[2] 崔文玉[2] 龙超良[2] 段炼[3] 汪海[2,4] 

机构地区：[1]广西医科大学,南宁530021 [2]军事医学科学院卫生学环境医学研究所心血管药物研究中心,北京100850 [3]军事医学科学院附属医院,北京100071 [4]北京赛德维康医药研究院,北京100039

出　　处：《中国应用生理学杂志》2013年第3期205-208,共4页Chinese Journal of Applied Physiology

基　　金：国家新药创制科技重大专项(2010 ZX 09401-307-1-9);军队“十二五”重大专项(AWS11J003);国家973计划(2009CB521804)

摘　　要：目的:观察ATP敏感性钾通道开放剂埃他卡林(Ipt)对异丙肾上腺素(ISO)致大鼠心室重构的保护作用。方法:采用多点皮下注射ISO致大鼠心室重构,连续灌胃给药Ipt 3 mg/(kg.d)6周,RM-6000八导生理记录仪测定大鼠血流动力学参数,称量计算心脏重量指数,采用HE染色观察心肌组织病理学的改变,Masson’s染色检测心肌间质胶原容积,比色法测定心肌组织中羟脯氨酸(Hyp)的含量,放射免疫法测定血浆中内皮素-1(ET-1)和前列环素(PGI2)含量。结果:ISO皮下注射完,经过6周后,与正常对照组相比,模型组的心功能明显受损,其心室重构的特征包括心脏指数、心肌细胞横截面积、心肌纤维化程度、心肌组织Hyp含量显著增高;血浆中ET-1含量明显升高,PGI2含量明显降低;Ipt治疗6周后可显著逆转心室重构,降低ET-1含量,升高PGI2含量。结论:Ipt可逆转ISO诱导大鼠心室重构,其机制可能与Ipt保护内皮细胞功能,调节ET-1和PGI2系统的功能平衡相关。Objective：To study the effects of iptakalim（Ipt）,an ATP-sensitive potassium channel opener,on cardiac remodeling induced by isoproterenol（ISO） in Wistar rats.Methods： ISO was given subcutaneously（85 mg/（kg·d）,sc,7 days） to induce cardiac remodeling in rats.The rats in Ipt treated group were administrated with Ipt 3 mg/kg（po） after ISO injection.After treated with Ipt for 6 weeks,the hemodynamic parameters were tested by an eight channel physiological recorder（RM-6000）.Then the heart weight was weighed and the cardiac remodeling index was calculated.HE stain and Masson＇s stain were employed to perform histological analysis,the hydroxyproline（Hyp） content in cardiac tissue was detected by colorimetric method,radioimmunoassay was used to measure the plasma levels of endothelin-1（ET-1） and prostacyclin（PGI2）.Results： Six weeks after ISO injection, the cardiac functions of model group were damaged markedly compared with those of normal group.The characteristics of ventricular remodeling in model group included that the heart weight index,myocyte cross-sectional area,myocardial fibrosis,and the hydroxyproline content in cardiac tissue were all increased significantly.The plasma level of ET-1 was increased,while the plasma level of PGI2 was decreased significantly.These changes could be reversed by Ipt treatment（3 mg/（kg·d） for 6 weeks）.Conclusion： Ipt can reverse cardiac remodeling induced by isoproterenol in rats.The endothelial protective effect regulating effects of Ipt on the balance between the ET-1 and PGI2 system may be involved in its mechanisms.

关 键 词：埃他卡林 异丙肾上腺素 心室重构 ET-1 PGI2 

分 类 号：R332[医药卫生—人体生理学]