CFTR氯通道调控多囊卵巢综合征患者血小板活化及炎症的机制研究  

Mechanism of regulating platelet activation and inflammation in patients with polycystic ovary syndrome by CFTR chloride channels

作　　者：陈冬梅[1] 钟晓珠 梁伟莹 刘耀升 陈圣福 谢梅青[1] Chen Dongmei;Zhong Xiaozhu;Liang Weiying(Department of Obstetrics and Gynecology,Sun Yat-sen Memorial Hospital of Sun Yat-sen University,Guangzhou 510120)

机构地区：[1]中山大学孙逸仙纪念医院妇产科,广州510120 [2]中山大学中山医学院药理学教研室和心脑血管研究中心,广州510080

出　　处：《现代妇产科进展》2024年第11期838-842,846,共6页Progress in Obstetrics and Gynecology

基　　金：广东省自然科学基金面上项目(No:2024A1515013191);广东省医学科研基金(No:A2023339)。

摘　　要：目的:研究CFTR氯通道调控多囊卵巢综合征(PCOS)患者血小板活化及炎症的机制。方法:选取2021年4月至2021年10月在中山大学孙逸仙纪念医院妇科门诊患者,满足PCOS诊断标准及对照组的纳排标准后,利用PCOS患者血样、体外细胞模型、基因干预CFTR等手段,探讨CFTR调控PCOS血小板活化的机制。结果:与月经规律女性相比,PCOS患者的月经周期,血清LH、PRL、T以及0、1、2h胰岛素和血糖均存在明显差异(P<0.001)。PCOS患者血小板中,CFTR蛋白表达水平降低,且PCOS患者的血小板活化指标P-selectin表达显著高于对照组,且与CFTR表达呈负相关;同时CFTR表达与HOMA-IR、睾酮水平呈负相关。PCOS组血小板的胞内氯浓度显著高于对照组(P<0.001),同时SGK1的磷酸化(Ser422)增加。MEG-01细胞中,相较对照组,过表达CFTR后,SGK1的磷酸化及P2Y12表达降低、胞内氯浓度下降(P<0.05)。MEG-01细胞中,相较于对照组,敲低SGK1后,P2Y12表达降低、血小板炎症指标下降(P<0.05)。结论:PCOS患者的血栓发生风险增加,其可能原因是高雄及胰岛素抵抗导致PCOS患者血小板中CFTR蛋白表达下降,从而导致血小板的[Cl-]i升高,SGK1磷酸化水平升高,引起了血小板炎症因子P2Y12的升高,最终导致血小板活化增加,血栓风险增加。Objective:To study the mechanism of regulating platelet activation and inflammation in patients with polycystic ovary syndrome by CFTR chloride channels.Methods:Patients who met the diagnostic criteria for PCOS and the study criteria were selected from the gynecological clinic of Sun Yat-sen Memorial Hospital,Sun Yat-sen University from April 2021 to October 2021.Blood samples of PCOS patients,in vitro cell models,and gene intervention with CFTR were used to explore the mechanism of regulating platelet activation of PCOS by CFTR.Results:Compared with women in the control group,there were significant differences in menstrual cycle,serum LH,PRL,T,0,1,2h insulin and blood glucose in PCOS patients(P<0.01).In platelets of PCOS patients,the expression level of CFTR protein was decreased,and the expression of P-selectin in PCOS patients was significantly higher than that in control group,and was negatively correlated with the expression of CFTR.Meanwhile,the expression of CFTR was negatively correlated with HOMA-IR and testosterone levels.The intracellular chlorine concentration of platelets in PCOS group was significantly higher than that in control group(P<0.01),and the phosphorylation of SGK1(Ser422)was increased.In MEG-01 cells,phosphorylation of SGK1,expression of P2Y12 and intracellular chlorine concentration decreased after overexpression of CFTR compared with control group(P<0.05).In MEG-01 cells,compared with the control group,after knocking down SGK1,the expression of P2Y12 and platelet inflammation index were decreased(P<0.05).Conclusion:The increased risk of thrombosis in PCOS patients may be attributed to the decreased expression of CFTR protein in platelets caused by hyperandrogenism and insulin resistance,which leads to the increase of platelet[Cl-]i,the increase of SGK1 phosphorylation,the increase of platelet inflammatory factor P2Y12,thus activating platelets and promoting thrombosis.

关 键 词：多囊卵巢综合征 CFTR 胰岛素抵抗 高雄激素血症 血小板活化 

分 类 号：R711.75[医药卫生—妇产科学]