2025 年第 5 期 第 20 卷

垂体泌乳素腺瘤患者血清哺乳动物雷帕霉素靶蛋白水平和免疫功能指标与溴隐亭耐药性的相关性研究

Correlation between serum mammalian target of rapamycin level, immune function indexes and bromocriptine resistance in patients with pituitary prolactinoma

作者：张谦张诚高峰帕热哈提江·依孜木董军吴永刚

英文作者：Zhang Qian Zhang Cheng Gao Feng Parehatijiang Yizimu Dong Jun Wu Yonggang

单位：新疆维吾尔自治区人民医院神经外科中心，乌鲁木齐830002

英文单位：Neurosurgery Center People′s Hospital of Xinjiang Uygur Autonomous Region Urumqi 830002 China

关键词：垂体泌乳素腺瘤；哺乳动物雷帕霉素靶蛋白；免疫功能指标；溴隐亭；耐药性

英文关键词：Pituitaryprolactinoma;Mammaliantargetofrapamycin;Immunefunctionindexes;Bromocriptine;Resistance

• 摘要：

• 目的 探讨垂体泌乳素腺瘤患者血清哺乳动物雷帕霉素靶蛋白（mTOR）水平和免疫功能指标与溴隐亭耐药性的相关性。方法 选取2020年1月至2024年5月新疆维吾尔自治区人民医院收治的120例垂体泌乳素腺瘤患者作为研究对象。根据溴隐亭治疗反应将所有患者分为敏感组（78例）和耐药组（42例）。比较2组患者的临床资料、血清mTOR水平和免疫功能指标。分析血清mTOR和免疫功能指标的相关性。构建广义线性混合模型分析血清mTOR和免疫功能指标与溴隐亭耐药性的关系。采用限制性立方样条分析血清mTOR和免疫功能指标与溴隐亭耐药的剂量-反应关系。采用受试者工作特征曲线分析血清mTOR和免疫功能指标对溴隐亭耐药性的诊断效能。结果 mTOR水平与CD+3、CD+4以及CD+4/CD+8比值之间存在显著的负相关性，与CD+8之间存在显著的正相关性（均P＜0.05）。广义线性混合效应模型分析结果显示，随着mTOR和CD+8的升高，患者溴隐亭耐药性风险显著上升，随着CD+3、CD+4以及CD+4/CD+8比值的升高，患者溴隐亭耐药性风险显著降低。限制性立方样条模型结果显示，血清mTOR表达水平和免疫功能指标与溴隐亭耐药之间存在显著的非线性剂量-反应关系（P＜0.05）。血清mTOR联合免疫功能指标预测患者溴隐亭耐药性的曲线下面积为0.896（95%置信区间：0.627～0.985），敏感度和特异度分别为91.85%和92.53%。结论 在垂体泌乳素腺瘤患者中，血清mTOR水平与免疫功能指标之间存在显著的相关性，同时，这两者均被识别为溴隐亭耐药性的重要危险因素。

• Objective To investigate the correlation of serum mammalian target of rapamycin (mTOR) level and immune function indexes with bromocriptine resistance in patients with pituitary prolactinoma. Methods A total of 120 patients with pituitary prolactinoma admitted to the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2020 to May 2024 were selected as the research objects. According to the response to bromocriptine treatment, all patients were divided into sensitive group (78 cases) and resistant group (42 cases). The clinical data, serum mTOR level and immune function indexes of the two groups were compared. The correlation between serum mTOR and immune function indexes was analyzed. Generalized linear mixed model was constructed to analyze the relationship between serum mTOR, immune function indexes and bromocriptine resistance. Restricted cubic spline was used to analyze the dose-response relationship between serum mTOR, immune function indexes and bromocriptine resistance. Receiver operating characteristic curve was used to analyze the diagnostic efficacy of serum mTOR and immune function indexes in bromocriptine resistance. Results There was a significant negative correlation between mTOR level and CD+3, CD+4, and the CD+4/CD+8 ratio, and a significant positive correlation between mTOR level and CD+8（all P＜0.05）. The results of generalized linear mixed model analysis showed that with the increase of mTOR and CD+8, the risk of bromocriptine resistance in patients increased significantly, and with the increase of CD+3, CD+4, and CD+4/CD+8 ratio, the risk of bromocriptine resistance in patients decreased significantly.The results of restricted cubic spline model showed that there was a significant nonlinear dose-response relationship between serum mTOR expression level and immune function indicators and bromocriptine resistance（P＜0.05）. The area under the curve of serum mTOR combined with immune function indicators to predict the resistance of patients with bromocriptine was 0.896 (95% confidence interval: 0.627-0.985), and the sensitivity and specificity were 91.85% and 92.53%, respectively. Conclusion In patients with pituitary prolactinoma, there is a significant correlation between serum mTOR level and immune function indicators, and both of them have been identified as important risk factors for bromocriptine resistance.