高血压相关性内皮型miRNAs的鉴定与功能分析及其对高血压的治疗价值研究

Our previous study showed that miRNAs play an important role in regulation of the expresssion of endothelial nitric oxide synthase (eNOS), a key gene related to cardiovascular diseases. To further explore the role of specific miRNA in the development of hypertension and its therapeutic value for this disease, the programe in this study is scheduled as follow : 1) the miRNA expression profiles in plasma of hypertension patients and fore-and-aft directional differentiation of endothelial cells will be analyzed by miRNA microarray, and the hypertension-related endomiRNAs(HRE-miRNAs) will be selected and identified; 2）select miR-24 as the representative of HRE-miRNAs, study its effect on vascular endothelial differentiation / proliferation and its role and the molecular mechanisms involved in regulating the expression of endothelial-speseifc gene eNOS、miR-24 target gene SP-1; 3)to probe the therapeutic effect of endomiRNAs on hypertension, mice of NOS-inhibited hypertension model will be used to study the regulational effects of miR-24 and its inhibitor on blood pressure. Accomplishment of of this stduy will be helpful to explore the role of endomiRNAs in regulating expression of the key genes related to cardiovascular diseases, and be important theoretical value to sduty their role in development of hypertension. It will be of great clinical significance to search for endomiRNAs as the novel molecular drug for hypertension therapy.

前期研究表明微核糖核酸（miRNAs）对心血管疾病关键性基因内皮型一氧化氮合酶（eNOS）表达有重要的调节作用。为进一步探讨特异性miRNA在高血压病发生发展中的作用及其治疗价值，本项目拟：1）用miRNA芯片对高血压病人血浆、定向内皮细胞分化前后的miRNA表达谱进行分析，筛选和鉴定高血压相关性内皮型miRNAs；2）选miR-24为代表构建其表达质粒，研究其对血管内皮细胞分化/增殖的影响以及对内皮特异性基因eNOS、miR-24靶基因SP-1表达的调节作用和分子机制；3）用NOS抑制型高血压模型小鼠，研究miR-24及其抑制剂对血压的调节作用，以探讨内皮型miRNAs对高血压的治疗效果。该项目的完成有助于探讨内皮型miRNAs对心血管疾病关键性基因表达调节、在高血压病发生发展中的作用具有重要的理论价值；寻找以内皮型miRNAs作为新型分子药物在高血压治疗的潜在价值具有重大的临床意义。

前期研究表明微核糖核酸（miRNAs）对心血管疾病关键性基因内皮型一氧化氮合酶（eNOS）表达有重要的调节作用。为进一步探讨特异性 miRNA 在高血压病发生发展中的作用及其治疗价值，本项目用临床病人标本、细胞培养体系和疾病动物模型等做了以下三个方面研究：1）用 miRNA 芯片对高血压病人血浆、定向内皮细胞分化前后的 miRNA 表达谱进行分析，筛选和鉴定高血压相关性内皮型 miRNAs；2）选 miR-24、miR-21和27nt-miRNA 为代表构建其表达质粒，研究其对血管内皮细胞分化/增殖的影响以及对内皮特异性基因 eNOS、miR-24 靶基因SP-1 表达的调节作用和分子机制；同时，我们对血管平滑肌细胞、肿瘤细胞和脂肪细胞的增殖和分化等也做了类似观察和研究；3）用高血压模型小鼠，研究miR-24 和27nt-miRNA及其抑制剂对血压的调节作用，以探讨内皮型miRNAs 对高血压治疗的潜在价值。该项目已经如期完成。本研究结果表明：内皮型miRNAs 对心血管疾病关键性基因表达调节及其在高血压病发生发展中起着重要的调节作用，具有重要的理论价值；某些内皮型miRNAs 作为新型分子药物在高血压治疗可能具有重大的潜在价值。