心力衰竭是由于任何原因的初始心肌损伤(心肌梗死、血液动力负荷过重、炎症等)，引起心肌结构和功能的变化，最后导致心室泵血功能低下。心力衰竭是一种进行性的病变，一旦起始以后，即使没有新的心肌损害，临床亦处于稳定阶段，仍可自身不断发展（很无奈）。导致心力衰竭发生发展的基本机制是心室重塑，这是由于一系列复杂的分子和细胞机制导致心肌结构、功能和表型的变化。

最近临床研究发现提高心肌细胞内钙离子水平（有双面性，可引起损伤）能提高心肌收缩能力，可能是一种有效治疗方法。MicroRNA在心衰是出现异常变化，但这种变化是否影响到心肌收缩功能，以及是否可以作为治疗的目标扔不清楚。首先利用高通量功能筛选的人类microRNA组学技术，以和肌浆网钙吸收泵mRNA相互作用为指标，筛选出具有抑制心肌细胞内钙离子处理功能的microRNA 875条，对这875条microRNA进行研究，发现miR-25能延缓心肌细胞钙吸收，心衰动物和患者miR-25都上调，腺病毒介导miR-25高表达能导致心脏收缩功能下降，注射miR-25反义寡核苷酸能纠正小鼠心衰，提高心脏功能和存活率。

本研究来自加州大学，文章今天发表在《自然》杂志。值得关注的是miR-25不仅可以作为治疗的目标，也可以作为诊断标记。研究思路方面，采用高通量筛选，寻找目标分子，然后用常规方法鉴定功能，从大的方面看，思路比较清晰简洁流畅。

Anti-miR-25 or control (scrambled sequence) anti-miRNA was administered intravenously to sham-operated wild-type mice (Sham) or to unoperated Serca2a-cardiomyocyte null (S2a KO) mice³⁸, as for the experiments in Fig. 4 (see Methods). Sham-operated animals were injected with anti-miRNAs 1 week after surgery and followed by echocardiography. S2a KO animals were generated by injection with 4-OH tamoxifen intraperitoneally for 4 days (see Methods) to delete Serca2a, then injected with anti-miRNAs 1 week later and followed by echocardiography. a, Representative two-dimensional guided M-mode images of the LVs from wild-type and S2a KO mice. b, c, Echocardiographic indices of left ventricular inner dimension during diastole, LVIDd (b), and systole, LVIDs (c) (n = 3 (sham plus control); 8, (sham plus anti-miR-25); 7 (S2a KO plus control); 11 (S2a-KO plus anti-miR-25) 4 weeks after control or anti-miRNA injection. d, Echocardiographic measurement of fractional shortening (FS) expressed as a percentage at time points after control or anti-miRNA injection (n = 4 (sham plus control); 3 (sham plus anti-miR-25); 3 (S2a KO plus control); 3 (S2a KO plus anti-miR-25)). S2a KO mice show characteristic dilation and decline in cardiac function after 4-OH tamoxifen-induced excision of Serca2a³⁹. ***P < 0.001 (Student’s t-test for difference between S2a KO and sham-operated control anti-miRNA groups at week 4 after injection). e, Haemodynamic effect of anti-miR-25 and control anti-miRNA injection is represented by pressure–volume plots of treatment cohorts as indicated 4 weeks after injection of control or anti-miRNA. Note that specific anti-miR-25 and control anti-miRNA acted similarly in sham-operated wild-type animals (n = 3 (sham plus control); 3, (sham plus anti-miR-25); 2 (S2a KO plus control); 3 (S2a-KO plus anti-miR-25). Moreover, anti-miR-25 did not increase cardiac function of S2a KO mice, unlike TAC-operated wild-type mice (Fig. 4), suggesting that the beneficial effect on cardiac function depends on SERCA2a. Data are represented as mean ± s.e.m. n = number of biological replicates (all included). NS, not significant.