miRNA-214靶向作用于钙网蛋白保护阿霉素相关大鼠心肌损伤

Protective effect of miRNA-214 targeting calreticulin on adriamycin-related myocardial injury in rats

目的:探讨miRNA-214对阿霉素相关大鼠心肌损伤的保护作用及其相关机制。方法:SD大鼠随机分为对照组、阿霉素心肌损伤模型组(模型组)和miRNA-214转染组;用超声心动图检测3组大鼠心功能相关指标;用PCR检测3组大鼠心肌细胞miRNA-214的表达差异;用免疫印迹检测心肌组织钙网蛋白的表达水平。结果:miRNA-214转染组全心质量、左心室质量显著高于模型组,但低于对照组;miRNA-214转染组全心肥厚指数、左心室肥厚指数显著低于模型组,但高于对照组。miRNA-214转染组心肌纤维破坏程度较模型组显著减轻,肌纤维完整,横纹排列整齐,有少许中性粒细胞浸润与无空泡变性。miRNA-214转染组大鼠心肌细胞中miRNA-214相对表达量显著高于模型组,但低于对照组。miRNA-214转染组谷丙转氨酶、谷草转氨酶、乳酸脱氢酶、肌酸激酶、B型利钠肽水平显著低于模型组,但高于对照组。miRNA-214转染组左心室收缩末期内径、左心室舒张末期内径显著低于模型组,但高于对照组;miRNA-214转染组左心室短轴缩短率、左心室射血分数显著高于模型组,但低于对照组。miRNA-214转染组钙网蛋白表达量显著低于模型组,高于对照组。结论:miRNA-214可通过下调钙网蛋白缓解心肌损伤,有望成为一个新的治疗靶标。

Objective:To investigate the protective effect and related mechanism of miRNA-214 on adriamycinrelated myocardial injury.Methods:SD rats were randomly divided into control group,model group and miRNA-214 transfection group.Cardiac function related indexes were detected by echocardiography.At the end of the experiment,the rats were sacrificed and the expression of miRNA-214 was detected by PCR.The expression of calreticulin in myocardial tissue was detected by Western blotting.Results:miRNA-214 total heart mass and left ventricular mass in the transfected group were significantly higher than those in the model group,but lower than those in the control group.The whole heart fat thickness index and left ventricular hypertrophy index of miRNA-214 transfection group were significantly lower than those of the model group,but higher than those of the control group.Compared with the model group,the degree of myocardial fiber destruction in the miRNA-214 transfection group was significantly reduced,the muscle fiber was intact,the rhabdom was arranged neatly,and there was a little neutrophil infiltration and no vacuolar deformation.The relative expression of miRNA-214 in cardiomyocytes of rats in the miRNA-214 transfection group was significantly higher than that in the model group but lower than that in the control group.The levels of alanine aminotransferase,aspartate aminotransferase,lactic dehydrogenase,creatine kinase,and B type natriuretic peptide in the miRNA-214 transfection group were significantly lower than those of the model group,but higher than those of the control group.The left ventriular end-systolic diameter and left ventriular end-diastolic diameter in miRNA-214 transfection group were significantly lower than those of the model group,but higher than those of the control group.The left ventricular fractional shortening and left ventricular ejection fraction in miRNA-214 transfection group were significantly higher than those of the model group,but lower than those of the control group.The expression of calreticulin in the miRNA-214 transfection group was significantly lower than the model group and higher than the control group.Conclusion:miRNA-214 can attenuate myocardial injury by down-regulating calreticulin and is expected to become a new therapeutic target.