miR-133a在小鼠放射性心脏损伤中的作用

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

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20 Gy,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。

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 20 Gy 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.