原发性卵巢功能不全患者血清miRNA-146、OX-LDL和ROS的表达及临床意义  

Clinical significance of serum miRNA-146,OX-LDL and ROS expression in patients with primary ovarian insufficiency

作　　者：刘彦慧[1] 刘佳楠 熊符[2] 孙妍[1] 罗建华[1] 何珮清 何凤屏 Liu Yanhui;Liu Jia′nan;Xiong Fu;Sun Yan;Luo Jianhua;He Peiqing;He Fengping(Dongguan Maternal and Child Health Care Hospital,Dongguan,Guangdong 523110,China;College of Basic Medicine,Southern Medical University,Guangzhou,Guangdong 510515,China)

机构地区：[1]东莞市妇幼保健院,广东523110 [2]南方医科大学基础医学院遗传教研室,广州510515

出　　处：《中华医学遗传学杂志》2022年第11期1211-1215,共5页Chinese Journal of Medical Genetics

基　　金：广东省基础与应用基础研究基金区域重点项目(2020B1515120009)。

摘　　要：目的探讨原发性卵巢功能不全(primary ovarian insufficiency,POI)患者miRNA-146、氧化低密度脂蛋白(oxidized low density lipoprotein,OX-LDL)、活性氧(reactive oxygen species,ROS)的表达及临床意义。方法100例POI患者作为观察组,随机匹配100例卵巢功能正常的妇女作为对照组。通过荧光定量PCR(real-time PCR,qRT-PCR)检测血清miRNA-146,酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)检测OX-LDL和ROS,超声评估卵巢体积和卵巢动脉收缩期峰值血流速度。miRNA-146模拟物或抑制剂转染小鼠卵巢颗粒细胞,与OX-LDL共培养,评估其细胞活力、集落形成能力、细胞凋亡率和Toll样受体4(toll like receptor 4,TLR4)/核因子-κB(nuclear factor-κB,NF-κB)通路蛋白的表达。结果与对照组相比,POI组miRNA-146表达水平显著下降(P<0.05),OX-LDL和ROS表达水平显著升高(P<0.05),卵巢体积显著缩小(P<0.05),卵巢动脉收缩期峰值血流速度显著下降(P<0.05)。OX-LDL呈剂量依赖性抑制颗粒细胞活性,上调miRNA-146表达可增加卵巢颗粒细胞活力和集落数,降低其凋亡率和TLR4/NF-κB表达水平。结论miRNA-146可能靶向调控下游TLR4/NF-κB信号通路,影响OX-LDL和ROS诱导的POI氧化应激和炎症反应。miRNA-146有望成为早期预测POI的生物标志物和治疗新靶点。Objective To investigate the clinical significance of miRNA-146,OX-LDL and ROS in patients with primary ovarian insufficiency(POI).Methods 100 patients with POI were prospectively collected and 100 women with normal ovarian function were randomly selected as control group.Serum miRNA-146 expression level was detected by qRT-PCR and serum OX-LDL and ROS expression levels were detected by ELISA.Ovarian granulosa cells of mouse were transfected with miRNA-146 mimics or inhibitors,and then treated with OX-LDL.Cell viability,colony forming ability,apoptosis rate and toll like receptor 4(TLR4)/nuclear factor-κB(NF-κB)of pathway proteins were evaluated respectively.Results Compared with control group,the expression level of miRNA-146 in POI group was significantly lower,the expression level of OX-LDL and ROS were significantly higher,and the ovarian volume and peak systolic blood flow velocity of ovarian artery were significantly decreased in POI group.Upregulation of miRNA-146 expression had a protective effect on OX-LDL-injured ovarian granulosa cells,as evidenced by increased ovarian granulosa cell viability and colony number,reduced apoptosis,and downregulation of TLR4/NF-κB expression.Conclusion miRNA-146 can target downstream TLR4/NF-κB signaling pathway affects oxidative stress and inflammatory response of POI induced by OX-LDL and ROS,and is expected to become a biomarker for early prediction of POI and a new target for treatment.

关 键 词：早发性卵巢功能不全 miRNA-146 氧化低密度脂蛋白 活性氧 

分 类 号：R711.75[医药卫生—妇产科学]