【摘要】 目的 研究长链非编码RNA(long non-coding RNA,lncRNA)母源表达基因3(maternally expressed gene 3,MEG3)通过吸附微小RNA-21(microRNA-21,miR-21)减轻卵巢切除术(ovariectomy, OVX)大鼠心肌缺血再灌注(ischemia reperfusion, IR)损伤的作用及机制。方法 选择雌性SD大鼠108只，其中48只随机分为假手术组、OVX组、IR组、联合1组(OVX+IR),每组12只；其余60只OVX及心肌IR造模前尾静脉注射阴性对照、lncRNA MEG3、miR-21腺相关病毒，根据造模及腺相关病毒注射情况分为阴性假手术组、阴性模型组、lncRNA MEG3组、miR-21组、联合2组(lncRNA MEG3+miR-21),每组12只。检测心肌梗死面积、左心室射血分数(left ventricular ejection fraction, LVEF)、左心室短轴缩短率(left ventricular fractional shortening, LVFS)、血清乳酸脱氢酶(lactate dehydrogenase, LDH)、肌酸激酶(creatine kinase, CK)、肌酸激酶同工酶(creatine kinase isoenzyme, CK-MB)、心肌细胞凋亡率及裂解型半胱氨酸天冬氨酸蛋白酶3(cysteinyl aspartate specific proteinase-3,Caspase-3)表达。培养心肌H9c2细胞，采用双荧光素酶报告基因实验检测lncRNA MEG3靶向miR-21。结果 与假手术组比较，OVX组、IR组和联合1组心肌lncRNA MEG3表达明显降低，miR-21表达明显升高(P<0.05);与OVX组及IR组比较，联合1组lncRNA MEG3表达明显降低，miR-21表达明显升高，差异有统计学意义(P<0.05)。与阴性模型组比较，lncRNA MEG3组心肌梗死面积、血清LDH、CK、CK-MB、心肌细胞凋亡率、裂解型Caspase-3表达明显降低，LVFS、LVEF明显升高(P<0.05);与lncRNA MEG3组比较，联合2组心肌梗死面积、血清LDH、CK、CK-MB、心肌凋亡率、裂解型Caspase-3表达明显升高，LVFS、LVEF明显降低[(43.58±3.32)%vs(50.37±4.29)%,(57.12±4.28)%vs(68.47±5.61)%,P<0.05]。结论 过表达lncRNA MEG3通过吸附miR-21减轻OVX大鼠心肌IR损伤。更多还原

【Abstract】 Objective To investigate the effect and mechanism of long non-coding RNA(lncRNA) maternally expressed gene 3(MEG3) on the alleviation of myocardial ischemia-reperfusion(IR) injury by sponging miR-21 in rats after ovariectomy(OVX).Methods A total of 108 female SD rats were subjected, and 48 of them were randomly divided into sham group, OVX group, IR group and combined group 1(OVX+IR),with 12 rats in each group.And the remaining 60 rats were given an injection with blank adeno-associated virus(AAV,negative control),lncRNA MEG3 AAV and miR-21 AAV,respectively through the tail vein before OVX and myocardial IR modeling, and then consequently assigned into negative sham group, negative model group, lncRNA MEG3 group, miR-21 group, and combined group 2(lncRNA MEG3+miR-21),with 12 rats in each group.Myocardial infarction size, left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),serum lactate dehydrogenase(LDH),creatine kinase(CK),creatine kinase isoenzyme(CK-MB) content, cardiomyocyte apoptotic rate and expression level of cleaved Caspase-3 were determined.Dual luciferase reporter gene assay was used to detect lncRNA MEG3 targeting miR-21 in H9c2 cardiomyocytes.Results Compared with the sham group, the expression of lncRNA MEG3 was decreased and that of miR-21 was increased in the OVX group, IR group and combined group 1(P<0.05).The combination group 1 had significantly lower lncRNA MEG3 expression and higher miR-21 expression than the OVX group and IR group(P<0.05).Compared with the negative model group, the myocardial infarction size, serum LDH,CK,CK-MB,cardiomyocyte apoptotic rate, and cleaved Caspase-3 expression were decreased, while LVFS and LVEF were increased in the lncRNA MEG3 group(P<0.05).Compared with the lncRNA MEG3 group, myocardial infarction size, serum LDH,CK,CK-MB content, cardiomyocyte apoptotic rate, Cleaved Caspase-3 expression were increased, while LVFS and LVEF were decreased in the combined group 2 [(43.58±3.32)% vs(50.37±4.29)%,(57.12±4.28)% vs(68.47±5.61)%,P<0.05].Conclusion Overexpression of lncRNA MEG3 alleviates the myocardium IR injury in OVX rats by sponging miR-21.更多还原