miR-133a在小鼠放射性心脏损伤中的作用

目的 探讨microRNA对小鼠放射性心脏损伤(RIHD)的调节作用,为其治疗提供一个新策略。方法 基于Gene Expression Omnibus数据库的GSE147241数据集(包括正常心脏组织和照射心脏组织)进行生物信息学研究分析,以确定差异表达的基因。而后将30只雄性C57/BL6小鼠随机分为对照组、照射组、miR-133a过表达干预组。照射组和miR-133a过表达干预组心脏单次X线照射20Gy,对照组不照射,饲养16周。超声心动检查心功能,Masson染色法检测心肌纤维化,qRT-PCR法检测心肌miR-133a、CTGF mRNA、COL-1 mRNA、COL-3 mRNA的表达,蛋白印迹法检测心肌组织CTGF、COL-1、COL-3的蛋白表达水平。结果 miR-133a为照射组与对照组之间的差异基因。过表达miR-133a可以改善照射引起的心功能下降(P<0.01)和心肌间质胶原含量增多(P<0.01),且过表达miR-133a可以降低照射引起的CTGF、COL-1、COL-3的mRNA及蛋白表达水平的增加(P<0.01)。结论 照射使胶原蛋白合成增加致心肌纤维化重塑,而过表达miR-133a可以减少放射性心肌纤维化。

Role of miR-133a in radiation-induced cardiac injury in mice

Objective To investigate the regulatory role of microRNA in radiation-induced heart disease (RIHD) in mice and provide a new strategy for its treatment. Methods Based on the Gene Expression Omnibus database (GSE147241), which includes normal heart tissue and irradiation heart tissue, we conducted bioinformatics research and analysis to determine the differentially-expressed genes. Then, thirty male C57/BL6 mice were randomly divided into the control group, irradiation group and miR-133a overexpression intervention group. The heart received single dose of X-ray 20Gy in the irradiation group and miR-133a overexpression intervention group, but not in the control group, and then fed for 16 weeks. Cardiac function was assessed by echocardiography. Myocardial fibrosis was detected by Masson staining. The expression levels of miR-133a, CTGF, COL-1 and COL-3 mRNA were detected by qRT-PCR. The expression levels of CTGF, COL-1 and COL-3 proteins were detected by western blot. Results miR-133a was the differentially-expressed gene between the irradiation and control groups. Overexpression of miR-133a could mitigate the decrease in cardiac function and increase in myocardial collagen content (P<0.01). Meantime, overexpression of miR-133a could down-regulate the expression levels of CTGF, COL-1, COL-3 mRNA and protein (P<0.01). Conclusions Radiation increases the synthesis of collagen and leads to myocardial fibrosis remodeling. Overexpression of miR-133a can alleviate the radiation-induced myocardial fibrosis.