二氟甲基鸟氨酸对异丙肾上腺素诱导的心肌细胞肥大与凋亡的影响  

Effects of difluoromethylornithine on the cardiomyocytes hypertrophy and apoptosis induced by isoproterenol

作　　者：林岩[1,2,3] 肖薇[2] 李波[2] 金莉[2] 王国忠[2] 王珺[2] 赵雅君[4] 徐长庆[4] 刘吉成[1] 

机构地区：[1]齐齐哈尔医学院医药研究所,黑龙江齐齐哈尔161006 [2]齐齐哈尔医学院病理生理教研室,黑龙江齐齐哈尔161006 [3]黑龙江中医药大学中西医结合博士后流动站,黑龙江哈尔滨150040 [4]哈尔滨医科大学病理生理教研室,黑龙江哈尔滨150086

出　　处：《中国药理学通报》2015年第5期668-672,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81100170;81170178);黑龙江省教育厅面上项目(No 12521617);齐齐哈尔医学院科研基金资助项目(No QY2014Z-08)

摘　　要：目的探讨二氟甲基鸟氨酸(difluoromethylornithine,DFMO)对异丙肾上腺素(isoproterenol,ISO)诱导的心肌细胞肥大和凋亡的影响。方法实验分为4组:Control组、ISO组、ISO+DFMO组和ISO+DFMO+Pu组。利用ISO建立心肌细胞肥大模型,0.5 mmol·L-1DFMO和0.5 mmol·L-1腐胺预处理后检测ANP基因表达和心肌细胞表面积;检测各组细胞培养液中LDH活性和MDA含量,Annexin V/PI法检测心肌细胞凋亡率,real time-PCR和Western blot检测Bcl-2和Bax基因及蛋白表达。结果与ISO组相比,DFMO预处理后心肌细胞表面积和ANP基因表达降低(P<0.05),培养液中LDH和MDA释放量均下降(P<0.05),心肌细胞凋亡率降低(P<0.05);同时,DFMO上调Bcl-2基因和蛋白水平(P<0.05),上调Bcl-2/Bax比值(P<0.05),下调Bax基因和蛋白水平(P<0.05)。结论 DFMO对ISO诱导的心肌细胞肥大和凋亡有保护作用,其机制可能与Bcl-2和Bax表达有关。Aim To study the effects of difluoromethy-lornithine （DFMO）on cardiomyocytes hypertrophy and apoptosis induced by isoproterenol （ISO）.Methods The cardiomyocytes were divided into four groups ran-domly：Control group,ISO group,ISO＋DFMO group and （ISO ＋DFMO ＋Putrescine）group.The hyper-trophic model of cardiomyocytes was induced by ISO, the cardiomyocytes were pretreated with 0.5 mmol · L-1 DFMO and 0.5 mmol·L-1 putrine,the gene ex-pression of ANP,the surface area of cardiomyocytes and the contents of LDH and MDA were measured. Apoptotic value of cardiomyocytes was observed by An-nexin V/PI,the gene and protein expressions of Bcl-2 and Bax were detected by real-time PCR and Western＆nbsp;blot.Results Compared with ISO group,the cell sur-face area,the gene level of ANP,the apoptosis value of cardiomyocytes and the contents of LDH and MDA were decreased in ISO ＋DFMO group （P 〈0.05 ）. Meanwhile,DFMO pretreatment upregulated the gene and protein expressions of Bcl-2 （P 〈0.05 ）, in-creased the ratio of Bcl-2/Bax （P〈0.05 ）,downregu-lated the gene and protein levels of Bax （P〈0.05 ）. Conclusion The cardiomyocyte hypertrophy and ap-optosis induced by ISO can be protected by DFMO pre-treatment,which may be associated with the expression of apoptotic gene Bcl-2 and Bax.

关 键 词：多胺 二氟甲基鸟氨酸 心肌肥大 细胞凋亡 Bcl-2 BAX 

分 类 号：R-332[医药卫生] R322.11