参附汤提取物经miRNA-1调控HSP70表达对心力衰竭大鼠线粒体功能的影响

目的 研究参附汤提取物去甲乌药碱、人参皂苷Rg1是否经微小RNA-1（miRNA-1）调控热休克蛋白70（HSP70）调控心力衰竭大鼠线粒体功能。方法 选取100只Wistar大鼠，其中20只常规饲养，其余80只建立阿霉素诱导的心力衰竭大鼠模型，建模成功后分为4组，每组20只，即模型组、5mg/kg去甲乌药碱干预的HG组、5mg/kg人参皂苷Rg1干预的Rg1组以及去甲乌药碱联合人参皂苷Rg1干预的HG/Rg1组。4周后观察各组大鼠心功能、B型钠尿肽（BNP）、心肌组织中HSP70、线粒体功能指标三磷酸腺苷（ATP）、活性氧（ROS）、线粒体膜电位（MMP）、线粒体超微结构及心肌组织miRNA-1表达量。结果 与正常组比较，模型组、HG组、Rg1组、HG/Rg1组LVESD、LVEDD、LVESV、LVEDV、LVAWDd、LVAWDs、LVPWDd、LVPWDs、BNP、ROS水平、miRNA-1表达量升高，EF、FS、ATP、MMP、HSP70水平降低（P＜0.05）；与模型组相比，HG组、Rg1组、HG/Rg1组LVESD、LVEDD、LVESV、LVEDV、LVAWDd、LVAWDs、LVPWDd、LVPWDs、BNP、ROS水平、miRNA-1表达量降低，EF、FS、ATP、MMP、HSP70水平升高（P＜0.05）；与HG组、Rg1组相比，HG/Rg1组LVESD、LVEDD、LVESV、LVEDV、LVAWDd、LVAWDs、LVPWDd、LVPWDs、BNP、ROS水平、miRNA-1表达量降低，EF、FS、ATP、MMP、HSP70水平升高（P＜0.05）；HG组、Rg1组各指标比较，差异无统计学意义（P＞0.05）。结论 参附汤提取物去甲乌药碱联合人参皂苷Rg1可能经抑制miRNA-1上调HSP70而维护心力衰竭大鼠线粒体结构和功能不受破坏，从而保护心肌细胞。

Effects of Shenfu Decoction extract on mitochondrial function in rats with heart failure by regulating HSP70 expression via miRNA-1

Objective To investigate whether higenamine and ginsenoside Rg1 in Shenfu decoction extracts regulate mitochondrial function in rats with heart failure by regulating heat shock protein 70 (HSP70) through microRNA-1 (miRNA-1). Methods 100 Wistar rats were selected, 20 of them were routinely raised, and the remaining 80 rats were established with adriamycin-induced heart failure rat model. The HG group intervened with fenugreek, the Rg1 group intervened with 5 mg/kg ginsenoside Rg1, and the HG/Rg1 group intervened with higenamine combined with ginsenoside Rg1. After 4 weeks, the cardiac function, B-type natriuretic peptide (BNP), myocardial histopathology, HSP70 in myocardial tissue, mitochondrial function indexes adenosine triphosphate (ATP), reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were observed in each group. , mitochondrial ultrastructure and myocardial tissue miRNA-1 expression. Results Compared with the normal group, the levels of LVESD, LVEDD, LVESV, LVEDV, LVAWDd, LVAWDs, LVPWDd, LVPWDs, BNP, ROS, miRNA-1 expression in model group, HG group, Rg1 group, HG/Rg1 group increased, and the levels of EF, FS, ATP, MMP, HSP70 decreased (P<0.05); Compared with the model group, the levels of LVESD, LVEDD, LVESV, LVEDV, LVAWDd, LVAWDs, LVPWDd, LVPWDs, BNP, ROS and miRNA-1 in HG group, Rg1 group and HG/Rg1 group decreased, and the levels of EF, FS, ATP, MMP and HSP70 increased (P<0.05); Compared with HG group and Rg1 group, the levels of LVESD, LVEDD, LVESV, LVEDV, LVAWDd, LVAWDs, LVPWDd, LVPWDs, BNP, ROS, miRNA-1 expression in HG/Rg1 group decreased, and the levels of EF, FS, ATP, MMP, HSP70 increased (P<0.05); There was no significant difference between HG group and Rg1 group (P>0.05). Conclusion The combination of the extract of Shenfu decoction, noraconitine and ginsenoside Rg1 may protect the myocardial cells by inhibiting miRNA-1 to up regulate HSP70 and maintaining the structure and function of mitochondria in rats with heart failure.