基于PGC-1α/NRF-1/Tfam探讨芪珀生脉颗粒对HL-1心房肌细胞线粒体生物合成的改善作用

Improvement effect of Qipo Shengmai Granules on mitochondrial biosynthesis in HL-1 atrial myocytes based on PGC-1α/NRF-1/Tfam

目的研究芪珀生脉颗粒含药血清改善快速起搏诱导的HL-1心肌细胞线粒体功能障碍的机制。方法运用电刺激HL-1心房肌细胞,在体外建立快速起搏的心房颤动细胞模型。随后采用转染小干扰RNA(siRNA)沉默PGC-1α基因表达,并给予芪珀生脉颗粒含药血清或空白血清干预,通过检测线粒体数量、ATP合成能力及线粒体生物合成相关蛋白的表达,观察在PGC-1α基因沉默时,芪珀生脉颗粒是否能发挥对心肌细胞线粒体的保护及促进合成作用。结果芪珀生脉颗粒含药血清可以提高快速起搏的HL-1心肌细胞线粒体数量、ATP含量,上调线粒体生物合成相关的蛋白,转染PGC-1αsiRNA后,芪珀生脉颗粒的线粒体保护作用被阻断。结论芪珀生脉颗粒通过PGC-1α/NRF-1/Tfam介导的线粒体生物合成改善快速起搏HL-1心肌细胞线粒体功能障碍。

Objective To examine the improvement mechanism of mitochondrial biosynthesis in HL-1 cardiomyocytes mediated by fast pacing with Qipo Shengmai Granules(QPSM)contained serum.Methods An atrial fibrillation cell model with fast pacing was established in vitro by electrical stimulation of HL-1 atrial myocytes.Subsequently,the expression of PGC-1αgene was silenced by transfection of small interfering RNA(siRNA),and were treated with QPSM-contained serum or blank serum.By detecting the number of mitochondria,ATP synthesis ability and the expression of mitochondrial biosynthesis-related proteins,it was observed that when PGC-1αgene was silenced,whether QPSM could still play a role in protecting and promoting the synthesis of cardiomyocyte mitochondria.Results The QPSM-contained serum could increase the number of mitochondria and ATP content,and up-regulate the proteins related to mitochondrial biosynthesis in rapidly pacing HL-1 cardiomyocytes.After transfection with PGC-1αsiRNA,the mitochondrial protective effect of QPSM was blocked.Conclusion It is suggeted that QPSM may improve mitochondrial malfunction of fast paced HL-1 cardiomyocytes through PGC-1/NRF-1/Tfam-mediated mitochondrial biosynthesis.