miR-486参与OSAHS合并继发性红细胞增多症的发生

miR-486 is potentially associated with the occurrence of OSAHS comlicated with secondary polycythemia

目的探索miR-486在睡眠呼吸暂停低通气综合征(OSAHS)合并继发性红细胞增多症(SP)中的调控作用及临床意义。方法随机选取2020年5月至2021年4月在青海省人民医院门诊及健康体检中心就诊的汉族健康体检者25名作为对照组,于该院就诊的通过多导联睡眠监测及血常规确诊的30例OSAHS合并SP患者作为(OSAHS+SP)组,用RT-qPCR检测血单个核细胞miR-486、沉默信息调节因子1(Sirt1)、转录因子GATA-1及GATA-2 mRNA的表达,用ELISA检测血Sirt1的浓度。K562细胞经间歇性低氧(IH)、过表达或沉默miR-486处理后用RT-qPCR检测miR-486、Sirt1 mRNA的表达,用Western blot检测Sirt1的表达。K562细胞经沉默Sirt1后检测GATA-1 mRNA的表达。结果1)(OSAHS+SP)组患者体质指数、红细胞、血红蛋白及睡眠呼吸暂停指数均明显高于对照组(P<0.001);2)与对照组相比,(OSAHS+SP)组患者单个核细胞miR-486、GATA-1 mRNA表达均升高(P<0.001),而Sirt1 mRNA及蛋白表达均降低(P<0.001);3)(OSAHS+SP)组患者单个核细胞miR-486、GATA-1均与AHI和血红蛋白(HB)呈正相关(P<0.05)。单个核细胞Sirt1 mRNA表达、血浆Sirt1表达水平与AHI和HB均呈负相关(P<0.05);4)IH促进K562细胞miR-486表达(P<0.01),抑制Sirt1表达(P<0.01);过表达miR-486后Sirt1表达降低(P<0.01),而沉默miR-486后Sirt1表达升高(P<0.001);并且沉默Sirt1后GATA-1表达升高(P<0.01)。结论miR-486可能通过调控Sirt1表达参与OSAHS相关继发性红细胞增多症的发生。

Objective To explore the regulation and clinical significance of miR-486 in patients with sleep apnea-hypopnea syndrome(OSAHS) and secondary polycythemia. Methods Twenty-five healthy subjects who visited Outpatient Department and Health Examination Center of Qinghai Provincial People’s Hospital from May 2020 to April 2021 were elected as the control group, and thirty cases of OSAHS patients with secondary polycythemia diagnosed by polysomnography and laboratory examination were selected as the OSAHS+SP group. Peripheral blood mononuclear cell(PBMC) miR-486, Sirt1 and GATA-1 expression were measured by RT-qPCR, and the concen-tration of plasma Sirt1 was measured by ELISA. In addition, RT-qPCR was used for the miR-486,Sirt1 or expression in K562 cells after the IH treatment, miR-486 over-expression or miR-486 inhibition. The Sirt1 expression was measured by RT-qPCR and Western blot. GATA-1 mRNA expression was checked by RT-qPCR in Sirt1 inhibited K562 cells. Results 1)Body mass index, red blood cells, hemoglobin(HB) and sleep apnea index(AHI) in OSAHS+SP group were significantly higher than those of control group(P<0.001);2)The expression of miR-486, Sirt1, and GATA-1 were significantly increased and plasma Sirt1 concentration was significantly decreased in OSAHS+SP patients PBMC(P<0.001);3)PBMC miR-486 and GATA-1 expression were positively correlated with AHI and HB(P<0.05). PBMC Sirt1 expression and plasma Sirt1 level were negatively correlated with plasma Sirt1 concentration in OSAHS+SP group(P<0.05);4)IH promoted the expression of miR-486(P<0.01) and inhibited Sirt1 expression in K562 cells(P<0.01). RT-qPCR and Western blot showed that over-expression of miR-486 decreased Sirt1 expression(P<0.01), whereas miR-486 inhibition increased the expression of Sirt1(P<0.001). The GATA-1 expression was increased after the inhibition of Sirt1(P<0.01). Conclusions miR-486 regulates the biological process of OSAHS patients with secondary polycythemia by targeting at Sirt1.