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

摘要

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 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.%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－1 DFMO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。