心房颤动患者hsa-miR-4443的变化及其影响与机制

Expression of hsa-miR-4443 in patients with atrial fibrillation and its influence and underlying mechanism

目的探讨hsa-miR-4443在心房颤动患者中的变化及其可能的机制。方法选择2017年1月~2018年1月在本院就诊的患者100例,分为房颤组和对照组患者各50例,进行血清hsa-miR-4443水平、Ⅲ型原胶原N端前肽(PⅢNP)、Ⅰ型原胶原N端前肽(PINP)和Ⅰ型前胶原羧基端肽(PICP)水平测定。通过用hsamiR-4443模拟物和抑制剂转染心脏成纤维细胞(HCFBs),进行增殖、迁移、侵袭试验,寻找hsa-miR-4443的作用靶点和影响心房纤维化的信号通路。结果两组患者年龄、性别、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)差异无统计学意义(P>0.05)。房颤组患者C反应蛋白(CRP)、总胆固醇(TC)、三酰甘油(TG)、PINP、PICP、PⅢNP、左心房内径(LAD)明显高于对照组(P<0.05),而左室射血分数(LVEF)显著降低(P=0.008)。与对照组相比,房颤组患者血清hsa-miR-4443表达水平显著降低(P<0.001)。经miR-4443模拟物转染的HCFBs,其增殖、迁移和侵袭能力显著低于模拟物对照组(P<0.05)。经miR-4443抑制剂转染的HCFBs,其增殖、迁移和侵袭明显高于抑制剂对照组(P<0.05)。根据双荧光素酶检测结果显示:hsa-miR-4443可通过THBS1下调TGF-β1/α-SMA/胶原蛋白信号通路,促进HCFB纤维化改变。结论 hsa-miR-4443在心房颤动患者中表达水平下降,并参与调节心房纤维化来影响房颤。

Objective To explore the expression of hsa-miR-4443 in patients with atrial fibrillation(AF) and its influence and underlying mechanism. Method The serum hsa-miR-4443 levels, P Ⅲ NP、PINP and PICP levels of a total of 100 patients in our hospital from January 2017 to January 2018 were determined. The cardiac fibroblast(HCFBs) was transfected with hsa-miR-4443 mimics and inhibitors. The proliferation, migration and invasion assays were conducted to discover the target of hsa-miR-4443 and the signal pathway affecting AF. Results No significant difference was found in age, gender, low density lipoprotein(LDL-C) and high density lipoprotein(HDL-C) between the two groups(P > 0.05). C-reactive protein(CRP), total cholesterol(TC), triglyceride(TG), PINP, PICP, PIIINP and LAD in AF group were significantly higher than those in control group(P < 0.05), while LVEF was decreased significantly(P = 0.008). Compared with the control group, the expression of hsa-miR-4443 in serum in the AF group was significantly decreased(P < 0.001). The ability of proliferation, migration and invasion of HCFBs transfected with miR-4443 mimic was significantly lower than that of the control group(P < 0.05). The proliferation, migration and invasion of HCFBs transfected with miR-4443 inhibitor were significantly higher than those in the inhibitor control group(P < 0.05). According to the results of dual luciferase assay, hsa-miR-4443 can down-regulate the signal pathway of TGF-β 1/α-SMA/collagen via THBS1, thus promoting the fibrosis of HCFB. Conclusion The expression of hsami R-4443 is decreased in AF patients and hsa-mi R-4443 is involved in the regulation of atrial fibrosis to affect AF.