微小RNA-346抑制心肌细胞焦亡减轻大鼠心肌缺血再灌注损伤的作用机制

MiR-346inhibits myocardial cell pyroptosis to alleviate myocardial ischemia reperfusion injury in rats

目的 探讨微小RNA-346(miR-346)通过抑制心肌细胞焦亡减轻大鼠心肌缺血再灌注(IR)损伤的作用机制。方法 选择SPF级雄性SD大鼠24只,随机分为假手术组、IR组、空白转染组和高表达组(n=6),空白转染组及高表达组分别注射空白腺相关病毒、腺相关病毒miR-346预处理。采用免疫组织化学和Western blot法检测半胱氨酸天冬氨酸蛋白酶1(Caspase-1)、消皮素D(GSDMD)表达。结果 与假手术组比较,IR组miR-346表达明显降低(0.94±0.05 vs 3.00±0.13,P<0.05);与IR组比较,高表达组miR-346表达明显升高(2.21±0.27 vs 0.94±0.05,P<0.05)。与假手术组比较,IR组心肌损伤程度、Caspase-1和GSDMD表达明显升高(P<0.05);与IR组比较,高表达组心肌损伤程度、Caspase-1和GSDMD表达明显降低(P<0.05)。结论 miR-346可减轻大鼠心肌IR损伤程度,其机制可能与抑制心肌细胞焦亡Caspase-1/GSDMD信号途径有关。

Objective To investigate the mechanism of miR-346in reducing myocardial IR injury in rats by inhibiting myocardial pyroptosis.Methods Twenty-four SPF male SD rats were randomly divided into sham operation group,IR group,blank transfection group and high expression group(n=6).The blank transfection group and the high expression group were pretreated with injection of blank adeno-associated virus and adeno-associated virus miR-346,respectively.Immunohistochemical assay and Western blotting were used to detect the expression of Caspase-1and GSDMD.Results Compared with the sham operation group,the expression of miR-346was significantly decreased in the IR group(0.94±0.05 vs 3.00±0.13,P<0.05).And its expression level was obviously higher in the high expression group than the IR group(2.21±0.27 vs 0.94±0.05,P<0.05).The IR group had severer myocardial injury and increased expression of Caspase-1 and GSDMD when compared with the sham operation group(P<0.05).While,milder myocardial injury and notably decreased expression levels of Caspase-1and GSDMD were observed in the high expression group in comparison with the IR group(P<0.05).Conclusion MiR-346can reduce the severity of myocardial IR injury in rats,and the mechanism may be related to the inhibition of myocardial pyroptosis Caspase-1/GSDMD signaling pathway.