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目的:探讨microRNA-182(miR-182)、cAMP应答元件结合蛋白反式作用因子(CITED2)及低氧诱导因子-1(HIF-1)在缺血性心肌病(ICM)患者外周血中的表达及相关性。方法:收集本院46例ICM患者设为ICM组,同期选择32例健康者为对照组。分析2组一般资料及心脏功能指标[氨基末端B型脑钠肽前体(NTproBNP)、左室射血分数(LVEF)、6min步行实验(6MWT)距离];用实时荧光定量聚合酶链式反应法(qRT-PCR)检测血浆miR-182的含量,采用ELISA法测定血清CITED2和HIF-1水平,并观察ICM组治疗前及治疗3个月后上述指标的变化;分析ICM患者血浆miR-182水平与有关因素的相关性。结果:ICM组治疗前CITED2、LVEF及6MWT距离明显低于对照组,NT-proBNP、HIF-1及miR-182表达明显高于对照组,差异均有统计学意义(P<0.01)。与ICM组治疗前比较,ICM组治疗后CITED2、LVEF及6MWT距离明显升高,NT-proBNP、HIF-1及miR-182显著降低,差异均有统计学意义(P<0.01)。ICM组治疗前血浆miR-182的水平与CITED2、LVEF及6MWT距离成负相关(r=-0.427、-0.351、-0.298,P<0.05);ICM组治疗前血浆miR-182水平与HIF-1成正相关(r=0.337,P<0.05)。结论:外周血miR-182水平可作为ICM诊断及进行风险评估的生物标志物。miR-182可能通过其靶蛋白CITED2上调HIF-1,参与调控ICM的发生及发展。
Objective: To investigate the expression of miR-182, cAMP2, CITED2 and HIF-1 in peripheral blood of patients with ischemic cardiomyopathy (ICM) Expression and relevance. Methods: 46 ICM patients in our hospital were collected as ICM group and 32 healthy persons as control group. Two groups of general data and cardiac function index (NTproBNP, LVEF, 6MWT distance) were analyzed. The expression of GST-1 was detected by real-time fluorescence quantitative polymerase chain reaction The contents of miR-182 in plasma were detected by qRT-PCR. The levels of CITED2 and HIF-1 in serum were detected by ELISA. The changes of the above indexes were observed before and 3 months after treatment in ICM group. The correlation between the level and related factors. Results: The distance of CITED2, LVEF and 6MWT in ICM group was significantly lower than that in control group before treatment, and the expressions of NT-proBNP, HIF-1 and miR-182 were significantly higher in ICM group than those in control group (P <0.01). Compared with ICM group before treatment, the distance of CITED2, LVEF and 6MWT in ICM group was significantly increased, NT-proBNP, HIF-1 and miR-182 were significantly decreased (P <0.01). The level of plasma miR-182 in ICM group was negatively correlated with the distance of CITED2, LVEF and 6MWT (r = -0.427, -0.351, -0.298, P <0.05) (R = 0.337, P <0.05). Conclusion: The level of miR-182 in peripheral blood can be used as biomarker for ICM diagnosis and risk assessment. miR-182 may up-regulate HIF-1 through its target protein CITED2, which may be involved in the regulation of ICM development and progression.