摘要
MicroRNAs(miRNAs)基因芯片结果显示,携带有MYH7基因突变的家族性肥厚性心肌病病人的心脏组织以及小鼠心力衰竭模型中miR-30b表达下调,提示miR-30b可能在心脏疾病发生发展过程中发挥了重要功能.为研究miR-30b在心脏组织中的功能,本实验室首先建立了在心肌细胞特异性启动子琢肌球蛋白重链(琢-MHC,5.5 kb)控制下过表达miR-30b的转基因小鼠.通过qRT-PCR方法,证实miR-30b表达水平在转基因小鼠心脏组织中明显升高(P<0.05).miR-30b转基因小鼠心重/体重比和左心室/体重比无明显变化,心肌组织结构未见异常.目前,关于miR-30b在心肌梗死中的功能及相关机制未见报道.本文通过冠状动脉左前降支结扎法建立心肌缺血再灌注(ischemia-reperfusion,I/R)模型,以假手术组作为对照组.生化检测结果及TTC-Evans blue双染结果显示,I/R损伤后,与野生型小鼠相比,转基因小鼠LDH、CK-MB和cTn玉浓度显著减小(P<0.05),并且心肌梗死面积明显减少(P<0.05).超声心动图检测结果显示,转基因小鼠心功能显著改善.由此得出结论:miR-30b对缺血再灌注损伤的心肌具有保护作用,该研究成果可能为预防和治疗心肌梗死提供新策略.
MicroRNAs （miRNAs） array results have shown that the expression of miR-30b is downregulated in heart tissues from patients with familial hypertrophic cardiomyopathy who were carriers of missense mutations in the MYH7, and also in a murine heart failure model, implying that miR-30b might play an important role in heart diseases. To study miR-30b in vivo function, we generated a transgenic mouse line overexpressing miR-30b under the control of the 5.5 kb promoter of α-myosin heavy chain （α-MHC）. qRT-PCR results demonstrated that miR-30b was significantly increased in the heart tissues of miR-30b transgenic mice （P 〈 0.05）. miR-30b transgenic mice did not exhibit significant heart/body weight and left ventricular（LV）/body weight changes and abnormal myocardium structure. At present, little is known about how miR-30b regulates myocardial infarction. We constructed I/R models by the coronary artery ligation method and sham-operated mice were used as controls. Biochemical detection results and TTC-Evans blue results showed that after ischemia-reperfusion, these transgenic mice had lower releases of LDH, CK and cTnⅠ（P 〈 0.05）and their hearts exhibited a smaller infarct size compared to those from control mice（P 〈 0.05）. Echocardiographic results indicated that cardiac function of transgenic mice was markedly improved compared to that of control mice. In conclusion, miR-30b has protective effect upon ischemic-reperfusion injury. And it may provide a new therapeutic approach for preventing and treating myocardial infarction.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2014年第6期575-582,共8页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金资助项目(31010103911)~~
