We aimed to explore the regulatory mechanism of the axis of miR-223-3p-PIK3C2A-PI3K/Akt on cardiomyocyte apoptosis in rats with myocardial infarction. Thirty 8-week-old healthy male SD rats were used for establishing the sham group and the model group, with HE staining, TUNEL staining, and TTC staining performed. After the identification of the targeting relationship between PIK3C2A and miR-223-3p, experimental rats were randomly divided into seven groups by plasmid transfection, including the Blank group, negative control (NC) group, miR-223-3p mimic group, miR-223-3p inhibitor group, siRNA-PIK3C2A group, oe-PIK3C2A group, and miR-223-3p inhibitor + oe-PIK3C2A group. Four weeks after transfection, the expression levels of miR-223-3p and PIK3C2A in tissues as well as PI3K, Akt, Bax, and bcl-2 mRNA in cells were detected by qRT-PCR and western blot, in combination with the detection of apoptosis rate by flow cytometry. Compared with the sham group, the model group showed typical myocardial injury and abnormal staining, higher apoptotic index, and larger myocardial infarction area (all P < 0.05). PIK3C2A was the target gene of miR-223-3p. The expression level of miR-223-3p in model group was significantly lower than that in sham group, while the mRNA and protein expression levels of PIK3C2A increased significantly (all P < 0.05). In cell tests, the expression level of miR-223-3p increased significantly in miR-223-3p mimic group (P < 0.05), which, however, showed no significant change in siRNA-PIK3C2A group (P > 0.05). MiR-223-3p inhibitor group and siRNA-PIK3C2A group had obviously increased PI3K, Akt, mTOR and Bcl-2 mRNA, and protein expression, while decreased mRNA and protein expression of PIK3C2A and Bax (all P < 0.05); miR-223-3p mimic groups had the opposite trends (all P < 0.05). siRNA-PIK3C2A + miR-223-3p mimic showed no obvious change relative to the control groups (all P > 0.05). Low expression of miR-223-3p may downregulate PIK3C2A expression, resulting in the inhibition of myocardial cell apoptosis in rats with myocardial infarction via the activation of PI3K/Akt signaling pathway.

我们的目的是探讨miR-223-3p-PIK3C2A-PI3K/Akt轴对心肌梗死大鼠心肌细胞凋亡的调节机制。 30只8周龄健康雄性SD大鼠建立假手术组和模型组，进行HE染色、TUNEL染色、TTC染色。鉴定PIK3C2A与miR-223-3p的靶向关系后，通过质粒转染将实验大鼠随机分为7组，包括空白组、阴性对照（NC）组、miR-223-3p模拟组、miR-223-3p模拟组。 223-3p抑制剂组、siRNA-PIK3C2A组、oe-PIK3C2A组和miR-223-3p抑制剂+oe-PIK3C2A组。转染4周后,采用qRT-PCR和western blot检测组织中miR-223-3p、PIK3C2A以及细胞中PI3K、Akt、Bax、bcl-2 mRNA的表达水平,并结合流式细胞仪检测细胞凋亡率。与假手术组相比，模型组心肌损伤典型，染色异常，细胞凋亡指数较高，心肌梗死面积较大（均P < 0.05）。 PIK3C2A是miR-223-3p的靶基因。模型组miR-223-3p表达量显着低于假手术组，而PIK3C2A mRNA和蛋白表达量显着升高（均P < 0.05）。细胞测试中，miR-223-3p 模拟组 miR-223-3p 表达水平显着升高（ P < 0.05），而 siRNA-PIK3C2A 组 miR-223-3p 表达水平无明显变化（ P > 0.05）。 miR-223-3p抑制剂组和siRNA-PIK3C2A组PI3K、Akt、mTOR、Bcl-2 mRNA和蛋白表达量明显升高，PIK3C2A、Bax mRNA和蛋白表达量明显降低（均P < 0.05）； miR-223-3p模拟组具有相反的趋势（所有P <0.05）。 siRNA-PIK3C2A+miR-223-3p模拟物相对于对照组没有明显变化（均P >0.05）。 miR-223-3p低表达可能下调PIK3C2A表达，通过激活PI3K/Akt信号通路抑制心肌梗死大鼠心肌细胞凋亡。