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血清铁死亡相关指标与绝经后女性认知障碍的关系
王诺,汪玲,谷正盛,毕晓莹*
0
(海军军医大学(第二军医大学)第一附属医院神经内科, 上海 200433
*通信作者)
摘要:
目的 研究血清铁死亡相关指标与绝经后女性认知障碍的关系。方法 选择 2019 年 8 月至 2021 年12 月就诊于海军军医大学(第二军医大学)第一附属医院神经内科的女性 148 例,其中生育期 22 例、围绝经期 11 例、绝经后 115 例,比较 3 组女性的一般资料及血清铁死亡相关指标[谷胱甘肽过氧化物酶 4(GPX4)、还原型谷胱甘肽(GSH)、胱氨酸/谷氨酸反向转运体(Xc-系统)、酰基辅酶 A 合成酶长链家族成员 4(ACSL4)、活性氧(ROS)、脂质过氧化物(LPO)和丙二醛(MDA)]。根据蒙特利尔认知评估量表(MoCA)评分,将绝经后女性分为认知障碍组(77 例)和无认知障碍组(38 例),比较两组血清铁死亡相关指标,采用多重 logistic 回归模型分析绝经后女性认知障碍的影响因素,并通过 ROC 曲线评估影响因素对绝经后女性认知障碍的诊断价值。结果 与生育期和围绝经期女性相比,绝经后女性 MoCA 评分较低(均 P<0.05)。在生育期、围绝经期、绝经后女性中,血清 Xc-系统、GPX4、GSH、ACSL4、ROS、LPO 及 MDA 水平均逐渐升高, 3 组间比较差异有统计学意义(均 P<0.001)。与无认知障碍组相比,认知障碍组绝经后女性受教育年限短,血清 Xc-系统、GPX4、GSH、ACSL4、ROS、LPO 及 MDA水平均升高(均 P<0.05)。多重 logistic 回归分析显示受教育年限(OR=0.785, 95 % CI 0.662~0.930, P=0.005)和血清 GSH(OR=1.291, 95 % CI 1.087~1.534, P=0.004)是绝经后女性认知障碍的影响因素, ROC 曲线分析显示两者联合诊断认知障碍的 AUC 值为 0.764,灵敏度为 0.750,特异度为 0.676。结论 绝经后女性血清铁死亡相关指标 Xc-系统、GPX4、GSH、ACSL4、ROS、LPO 及 MDA 水平升高。血清 GSH 与女性认知障碍发生有关,其与受教育年限联合有望成为绝经后女性认知障碍早期诊断的潜在标志物。
关键词:  绝经后女性  认知障碍  铁死亡  铁代谢
DOI:10.16781/j.CN31-2187/R.20230667
投稿时间:2023-11-27修订日期:2024-01-29
基金项目:
Relationship between serum ferroptosis-related indexes and cognitive impairment in postmenopausal women
WANG Nuo,WANG Ling,GU Zhengsheng,BI Xiaoying*
(Department of Neurology, The First Affiliated Hospital of Naval Medical University(Second Military Medical University), Shanghai 200433, China
*Corresponding author)
Abstract:
Objective To explore the relationship between serum ferroptosis-related indexes and cognitive impairment in postmenopausal women. Methods A total of 148 women were selected from Department of Neurology of The First Affiliated Hospital of Naval Medical University (Second Military Medical University) from Aug. 2019 to Dec. 2021, including 22 cases in reproductive group, 11 in perimenopausal group, and 115 in postmenopausal group. The general information and serum ferroptosis-related indexes (glutathione peroxidase 4[GPX4], reduced glutathione[GSH], cystine/glutamate antiporter[system Xc-], acyl-CoA synthetase long-chain family member 4[ACSL4], reactive oxygen species (ROS), lipid hydroperoxide[LPO], and malondialdehyde[MDA]) of the 3 groups were compared. According to Montreal cognitive assessment (MoCA) score, the postmenopausal women were divided into cognitive impairment group (n=77) and non-cognitive impairment group (n=38). The levels of the serum ferroptosis-related indexes were compared between the 2 groups. Multiple logistic regression model was used to analyze the influencing factors of cognitive impairment in postmenopausal women. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of the influencing factors for cognitive impairment in postmenopausal women. Results Compared with the reproductive and perimenopausal groups, the MoCA score of the postmenopausal group was significantly lower (both P<0.05). The serum levels of system Xc-, GPX4, GSH, ACSL4, ROS, LPO and MDA were gradually increased in the reproductive, perimenopausal and postmenopausal groups, and the differences were significant (all P<0.001). Compared with the noncognitive impairment group, the educational years of the postmenopausal women was significantly shorter in the cognitive impairment group, and serum levels of system Xc-, GPX4, GSH, ACSL4, ROS, LPO and MDA were significantly higher (all P<0.05). Multiple logistic regression analysis showed that educational years (OR=0.785, 95 % confidence interval[CI]0.662-0.930, P=0.005) and serum GSH (OR=1.291, 95 % CI 1.087-1.534, P=0.004) were the influencing factors of cognitive impairment in postmenopausal women, and ROC curve analysis showed that area under curve of the combination in diagnosing cognitive impairment was 0.764, with a sensitivity of 0.750 and a specificity of 0.676. Conclusion The serum levels of ferroptosis-related indexes system Xc-, GPX4, GSH, ACSL4, ROS, LPO and MDA are increased in postmenopausal women. Serum GSH is associated with cognitive impairment, and its combination with educational years may be a potential marker for early diagnosis of cognitive impairment in postmenopausal women.
Key words:  postmenopausal women  cognitive impairment  ferroptosis  iron metabolism