血清NLRP3、IL-18水平与多囊卵巢综合征患者不孕的关系

Correlation study of serum NLRP3 and IL-18 levels with infertility in patients with polycystic ovary syndrome

摘要:

目的 探讨血清NOD样受体蛋白3（NLRP3）、白细胞介素-18（IL-18）水平与多囊卵巢综合征不孕的相关性。方法 选取2020年3月—2023年3月南开大学附属妇产医院和天津市第一中心医院收治的294例多囊卵巢综合征不孕患者作为研究组，280例输卵管异常、子宫内膜异位症等导致的不孕患者作为对照组。比较两组患者的临床资料；采用酶联免疫吸附试验检测血清NLRP3、IL-18水平；采用多因素逐步Logistic回归模型分析多囊卵巢综合征患者不孕的影响因素；采用受试者工作特征（ROC）曲线评估血清NLRP3、IL-18预测多囊卵巢综合征患者不孕的价值。结果 两组的年龄、不孕时间、吸烟、饮酒、收缩压、舒张压、总胆固醇、高密度脂蛋白、低密度脂蛋白、卵泡刺激素比较，差异均无统计学意义（P >0.05）。研究组体质量指数（BMI）、甘油三酯、胰岛素抵抗指数（HOMA-IR）、促黄体生成素及转铁蛋白均高于对照组（P <0.05）。研究组血清NLRP3、IL-18水平均高于对照组（P <0.05）。多因素逐步Logistic回归分析结果显示，血清NLRP3［O^R =4.293（95% CI：1.941，9.495）］，血清IL-18［O^R =4.104（95% CI：1.770，9.515）］，HOMA-IR［O^R =3.404（95% CI：1.477，7.846）］，BMI［O^R =3.391（95% CI：1.542，7.455）］是PCOS患者不孕的危险因素（P <0.05）。ROC曲线分析结果显示，血清IL-18、NLRP3及两者联合预测PCOS患者不孕的曲线下面积分别为0.748（95% CI：0.698，0.801）、0.844（95% CI：0.796，0.894）、0.905（95% CI：0.855，0.950）；血清IL-18、NLRP3及两者联合预测PCOS患者不孕的敏感性分别为66.32%（95% CI：0.572，0.746）、79.39%（95% CI：0.713，0.857）、88.53%（95% CI：0.844，0.934）；血清IL-18、NLRP3及两者联合预测PCOS患者不孕的特异性分别为70.68%（95% CI：0.623，0.799）、73.28%（95% CI：0.656，0.827）、86.32%（95% CI：0.830，0.908）。结论 血清NLRP3、IL-18水平升高与多囊卵巢综合征患者不孕密切相关，可作为预测多囊卵巢综合征患者不孕的生物学指标。

Abstract:

Objective To investigate the correlation between serum levels of NOD-like receptor protein 3 (NLRP3) and interleukin-18 (IL-18) and infertility in patients with polycystic ovary syndrome (PCOS).Methods From March 2020 to March 2023, a total of 294 infertile patients with PCOS were selected as the study group from Nankai University Affiliated Obstetrics and Gynecology Hospital and Tianjin First Central Hospital. Additionally, 280 infertile patients due to tubal abnormalities, endometriosis, and other causes were selected as the control group. Clinical data of the two groups were compared. Serum NLRP3 and IL-18 levels were measured using enzyme-linked immunosorbent assay (ELISA). Multivariate stepwise logistic regression analysis was used to identify factors influencing infertility in PCOS patients. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the predictive value of serum NLRP3 and IL-18 levels for infertility in PCOS patients.Results There were no significant differences between the two groups in terms of age, duration of infertility, smoking, alcohol consumption, systolic blood pressure, diastolic blood pressure, total cholesterol, high-density lipoprotein, low-density lipoprotein, and follicle-stimulating hormone (P > 0.05). The study group had higher body mass index (BMI), triglycerides, homeostasis model assessment of insulin resistance (HOMA-IR), luteinizing hormone, and transferrin levels compared to the control group (P < 0.05). Serum levels of NLRP3 and IL-18 were significantly higher in the study group (P < 0.05). Multivariate stepwise logistic regression analysis indicated that serum NLRP3 [O^R =4.293 (95% CI: 1.941, 9.495)], serum IL-18 [O^R =4.104 (95% CI: 1.770, 9.515)], HOMA-IR [O^R =3.404 (95% CI: 1.477, 7.846)], and BMI [O^R =3.391 (95% CI: 1.542, 7.455)] were risk factors for infertility in PCOS patients (P < 0.05). ROC curve analysis showed that the areas under the curve (AUC) for predicting infertility in PCOS patients using serum IL-18, NLRP3, and their combination were 0.748 (95% CI: 0.698, 0.801), 0.844 (95% CI: 0.796, 0.894), and 0.905 (95% CI: 0.855, 0.950), respectively. The sensitivities of serum IL-18, NLRP3, and their combination for predicting infertility in PCOS patients were 66.32% (95% CI: 0.572, 0.746), 79.39% (95% CI: 0.713, 0.857), and 88.53% (95% CI: 0.844, 0.934), respectively. The specificities were 70.68% (95% CI: 0.623, 0.799), 73.28% (95% CI: 0.656, 0.827), and 86.32% (95% CI: 0.830, 0.908), respectively.Conclusion Elevated serum levels of NLRP3 and IL-18 are closely associated with infertility in PCOS patients and can serve as biological markers for predicting infertility in this population.