Our experiments have previously demonstrated that rutin (RUT) can improve myocardial damage caused by pirarubicin (THP). However, the underlying molecular mechanisms remain uncertain. In this study, we developed an microRNA (miRNA) chip by replicating the rat model of THP‐induced myocardial injury and identified miR‐22‐5p and the RAP1‐member of RAS oncogene family/extracellular regulated protein kinases (RAP1/ERK) signaling pathway as an object of study. Also, in vivo experiments demonstrated that THP caused abnormal changes in the electrocardiogram, cardiac function, and histomorphology in rats (P < .01). THP also reduces the expression of miR‐22‐5p (P < .01) and increases the levels of RAP1/ERK signaling pathway‐related proteins (P < .01, P < .05). RUT significantly improved THP‐induced myocardial damage (P < .01), increased the expression of miR‐22‐5p (P < .01), and decreased the levels of RAP1/ERK signaling pathway‐related proteins (P < .01, P < .05). In vitro studies confirmed that Rap1a is one of the target genes of miR‐22‐5p. miR‐22‐5p overexpression in cardiomyocytes can affect the RAP1/ERK pathway and reduce reactive oxygen species production and cardiomyocyte apoptosis caused by THP (P < .01), which is consistent with the effect of RUT. Our results indicate that RUT treats THP‐induced myocardial damage, which may be achieved by upregulating miR‐22‐5p, causing changes in its target gene Rap1a and the RAP1/ERK pathway.

中文翻译：

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芦丁通过调节miR-22-5p调节的RAP1 / ERK信号通路来治疗吡柔比星引起的心肌损伤。

我们的实验先前证明，芦丁（RUT）可以改善吡柔比星（THP）引起的心肌损伤。但是，潜在的分子机制仍然不确定。在这项研究中，我们通过复制大鼠THP诱发的心肌损伤模型开发了microRNA（miRNA）芯片，并鉴定了miR-22-5p和RAS癌基因家族/细胞外调节蛋白激酶（RAP1 / ERK）的RAP1成员通路作为研究对象。另外，体内实验表明，THP引起大鼠心电图，心脏功能和组织形态的异常变化（P  <.01）。THP还降低了miR-22-5p的表达（P  <.01）并增加了RAP1 / ERK信号通路相关蛋白的水平（P  <.01，P <.05）。RUT显着改善了THP诱导的心肌损伤（P  <.01），增加了miR-22-5p的表达（P  <.01）和降低了RAP1 / ERK信号通路相关蛋白的水平（P  <.01，P  <.05）。体外研究证实Rap1a是miR-22-5p的靶基因之一。心肌细胞中miR-22-5p的过表达可影响RAP1 / ERK通路并减少由THP引起的活性氧生成和心肌细胞凋亡（P  <.01），这与RUT的作用一致。我们的结果表明RUT可治疗THP引起的心肌损伤，这可以通过上调miR-22-5p来实现，从而导致其靶基因Rap1a发生变化 和RAP1 / ERK途径。