Association between Peripheral Blood Gas6，IL-18BP and Secondary Cognitive Impairment Following Intracranial Aneurysm Surgery
-
摘要:
目的 探讨颅内动脉瘤患者外周血生长停滞特异性蛋白6（growth arrest-specific protein 6，Gas6）、白细胞介素18结合蛋白（interleukin-18 binding protein，IL-18BP）与术后继发认知功能障碍的关系，并分析其对术后继发认知功能障碍的预测价值。 方法 选取2022年1月至2025年5月盐城市第一人民医院287例颅内动脉瘤患者作为研究对象，均行介入手术治疗，依据术后3个月（失访3例）继发认知功能障碍情况将其分为认知障碍组82例、认知正常组202例。比较两组手术前后外周血Gas6、IL-18BP水平。分析颅内动脉瘤术后继发认知功能障碍的影响因素。分析外周血Gas6、IL-18BP与颅内动脉瘤术后继发认知功能障碍的关系。分析外周血Gas6、IL-18BP对颅内动脉瘤术后继发认知功能障碍的预测价值。 结果 认知障碍组术后1 d、术后3 d、术后7 d外周血Gas6水平高于认知正常组，IL-18BP水平低于认知正常组（P < 0.05）；校正了Hunt-Hess分级、CTFisher分级、动脉瘤最长径、手术时间、术后脑出血/脑缺血后，术后7 d外周血Gas6、IL-18BP仍与颅内动脉瘤术后继发认知功能障碍独立相关（P < 0.05）；术后7 d外周血Gas6水平与颅内动脉瘤术后继发认知功能障碍呈线性正相关，IL-18BP水平与颅内动脉瘤术后继发认知功能障碍呈线性负相关（P < 0.05）；术后7 d外周血Gas6、IL-18BP联合预测颅内动脉瘤术后继发认知功能障碍的AUC值明显高于单项指标预测（P < 0.05）。 结论 颅内动脉瘤患者外周血Gas6水平与术后继发认知功能障碍呈线性正相关，IL-18BP水平与术后继发认知功能障碍呈线性负相关，联合检测其水平对术后继发认知功能障碍具有一定预测价值。 -
关键词:
- 颅内动脉瘤 /
- 认知功能障碍 /
- 生长停滞特异性蛋白6 /
- 白细胞介素18结合蛋白 /
- 预测
Abstract:Objective To investigate the relationship between peripheral blood growth arrest-specific protein 6 （Gas6）, interleukin-18 binding protein （IL-18BP） and postoperative secondary cognitive impairment in patients with intracranial aneurysms, and to analyze its predictive value for postoperative secondary cognitive impairment. Methods A total of 287 patients with intracranial aneurysm who underwent endovascular intervention at Yancheng First People's Hospital from January 2022 to May 2025 were enrolled. Based on the presence or absence of postoperative secondary cognitive dysfunction at 3 months post-operation （3 cases lost to follow-up）, patients were divided into cognitive dysfunction group （n=82） and normal cognition group （n=202）. Peripheral blood levels of Gas6 and IL-18BP before and after surgery were compared between the two groups. The influencing factors of postoperative secondary cognitive dysfunction in intracranial aneurysm were analyzed. The relationship between peripheral blood Gas6, IL-18BP and postoperative secondary cognitive dysfunction in intracranial aneurysm was analyzed. The predictive value of peripheral blood Gas6 and IL-18BP for postoperative secondary cognitive dysfunction in intracranial aneurysm was analyzed. Results Peripheral blood Gas6 levels in the cognitive dysfunction group were higher at postoperative day 1, 3, and 7 compared with the normal cognition group, while IL-18BP levels were lower （P < 0.05）. After adjusting for Hunt-Hess grade, CT Fisher grade, maximum aneurysm diameter, operation time, postoperative cerebral hemorrhage/cerebral ischemia, peripheral blood Gas6 and IL-18 BP on postoperative day 7 remained independently associated with postoperative secondary cognitive dysfunction in intracranial aneurysm （P < 0.05）. Postoperative day 7 peripheral blood Gas6 levels were positively linearly correlated with postoperative secondary cognitive dysfunction in intracranial aneurysm, while IL-18BP levels were negatively linearly correlated （P < 0.05）. The area under the receiver operating characteristic curve （AUC） for combined prediction of postoperative secondary cognitive dysfunction using Gas6 and IL-18BP on postoperative day 7 was significantly higher than that of single indicators （P < 0.05）. Conclusion In patients with intracranial aneurysm, peripheral blood Gas6 levels are positively linearly correlated with postoperative secondary cognitive dysfunction, while IL-18BP levels are negatively linearly correlated. Combined detection of these biomarkers has predictive value for postoperative secondary cognitive dysfunction. -
图 1 外周血Gas6、IL-18BP与颅内动脉瘤术后继发认知功能障碍的线性关系
A：为Gas6；B：为IL-18BP。
Figure 1. Linear relationship between peripheral blood Gas6、IL-18BP and post-operative secondary cognitive impairment
图 2 外周血Gas6、IL-18BP预测颅内动脉瘤术后继发认知功能障碍的ROC曲线
Figure 2. ROC curve of peripheral blood Gas6 and IL-18BP in predicting secondary cognitive impairment after intracranial aneurysm surgery
表 1 两组人口学特征及生活习惯比较[（$\bar x \pm s $）/n（%）]
Table 1. Comparison of demographic characteristics between two groups [（$\bar x \pm s $）/n（%）]
资料 认知障碍组（n = 82） 认知正常组（n = 202） t/χ2 P 性别 0.420 0.517 男 40（48.78） 90（44.55） 女 42（51.22） 112（55.45） 年龄（岁） 62.38 ± 8.41 59.98 ± 10.22 1.883 0.061 受教育年限（年） 8.63 ± 2.68 9.16 ± 2.33 1.662 0.098 发病至入院时间（h） 6.52 ± 2.12 6.08 ± 1.74 1.809 0.071 生活习惯 吸烟史 35（42.68） 95（47.03） 0.444 0.505 饮酒史 28（34.15） 80（39.60） 0.737 0.391 基础疾病 高血压 57（69.51） 125（61.88） 1.476 0.224 糖尿病 30（36.59） 55（27.23） 2.435 0.119 高脂血症 38（46.34） 105（51.98） 0.742 0.389 
下载: 导出CSV
表 2 两组临床及手术相关指标比较[（$\bar x \pm s $）/n（%）]
Table 2. Comparison of clinical and surgery-relatedindicators between the two groups [（$\bar x \pm s $）/n（%）]
资料 认知障碍组（n = 82） 认知正常组（n = 202） t/χ2 P Hunt-Hess分级 24.895 <0.001* <Ⅲ级 45（54.88） 168（83.17） ≥Ⅲ级 37（45.12）* 34（16.83） CTFisher分级 37.888 <0.001* <Ⅲ级 40（48.78） 170（84.16） ≥Ⅲ级 42（51.22）* 32（15.84） 前循环动脉瘤 3.274 0.070 是 60（73.17） 125（61.88） 否 22（26.83） 77（38.12） 动脉瘤数目 0.742 0.389 单发 44（53.66） 97（48.02） 多发 38（46.34） 105（51.98） 动脉瘤最长径（ mm） 10.117 0.001# ≤10 52（63.41） 164（81.19） >10 30（36.59）# 38（18.81） 动脉瘤破裂 2.300 0.129 有 28（34.15） 51（25.25） 无 54（65.85） 151（74.75） 手术时间（min） 15.186 <0.001* ≤60 37（45.12） 141（69.80） >60 45（54.88） 61（30.20） 支架辅助治疗 0.945 0.331 有 45（54.88） 98（48.51） 无 37（45.12） 104（51.49） 术后脑血管痉挛 0.220 0.639 有 7（8.54） 14（6.93） 无 75（91.46） 188（93.07） 术后脑出血/脑缺血 7.653 0.006# 有 12（14.63）# 10（4.95） 无 70（85.37） 192（95.05） *P < 0.001；#P < 0.05。
下载: 导出CSV
表 3 两组手术前后外周血Gas6、IL-18BP水平比较（$\bar x \pm s $，pg/mL）
Table 3. Comparison of peripheral blood Gas6 and IL-18BP levels before and after surgery between the two groups （$\bar x \pm s $，pg/mL）
时间 组别 n 术前 术后1 d 术后3 d 术后7 d Gas6 认知障碍组 82 8.52 ± 1.45 15.38 ± 2.67a 13.47 ± 2.31ab 11.82 ± 1.79ab 认知正常组 202 8.48 ± 1.51 11.92 ± 2.14a 10.25 ± 1.39ab 9.52 ± 1.03ab F F组间=76.226，F时间=50.241，F交互=33.201 P P组间<0.001*，P时间<0.001*，P交互<0.001* IL-18BP 认知障碍组 82 650.38 ± 90.24 320.27 ± 56.42a 415.83 ± 65.22ab 549.83 ± 70.17ab 认知正常组 202 645.79 ± 88.25 468.41 ± 68.25a 552.94 ± 70.69ab 602.34 ± 78.92ab F F组间=85.936，F时间=71.215，F交互=44.185 P P组间<0.001*，P时间<0.001*，P交互<0.001* 与同组术前比较，aP < 0.05；与同组术后1 d比较，bP < 0.05；与同组术后3 d比较，cP < 0.05。
下载: 导出CSV
表 4 颅内动脉瘤术后继发认知功能障碍的影响因素
Table 4. Risk factors of secondary cognitive impairment following intracranial aneurysm surgery
变量 B S.E. Waldχ2 OR 95%CI P 下限 上限 模型1 常量 2.147 0.448 22.967 <0.001* Hunt-Hess分级 0.819 0.208 15.506 2.268 1.509 3.410 <0.001* CTFisher分级 0.820 0.179 20.983 2.270 1.599 3.225 <0.001* 动脉瘤最长径 0.664 0.197 11.347 1.942 1.320 2.857 <0.001* 手术时间 0.703 0.212 11.009 2.021 1.334 3.062 <0.001* 术后脑出血/脑缺血 0.815 0.252 10.461 2.259 1.379 3.702 <0.001* 术后7 d Gas6 0.476 0.121 15.453 1.609 1.269 2.040 <0.001* 术后7 d IL-18BP −0.147 0.040 13.447 0.864 0.798 0.934 <0.001* 模型2 常量 1.045 0.298 12.297 <0.001* 术后7 d Gas6 0.393 0.118 11.077 1.481 1.175 1.866 <0.001* 术后7 d IL-18BP −0.169 0.052 10.545 0.845 0.763 0.935 <0.001* 注：模型2在模型1基础上校正了Hunt-Hess分级、CTFisher分级、动脉瘤最长径、手术时间、术后脑出血/脑缺血比例。*P < 0.001；#P < 0.05。
下载: 导出CSV
表 5 外周血Gas6、IL-18BP对颅内动脉瘤术后继发认知功能障碍的预测价值
Table 5. Predictive value of peripheral blood Gas6 and IL-18BP for post-operative secondary cognitive impairment in intracranial aneurysm
指标 AUC 95%CI 约登指数 敏感度（%） 特异度（%） P 术后7 d Gas6 0.757 0.703～0.806 0.422 76.83 65.35 <0.001* 术后7 d IL-18BP 0.770 0.716～0.817 0.474 73.17 74.26 <0.001* 联合预测 0.862 0.816～0.900 0.600 74.39 85.64 <0.001* *P < 0.001。
下载: 导出CSV
-
[1] 方斯, 杨景云, 刘吉刚, 等. VWI-MRI评估颅内未破裂动脉瘤稳定性的价值研究[J]. 临床误诊误治, 2024, 37(6): 65-70. doi: 10.3969/j.issn.1002-3429.2024.06.013 [2] Wagner K, Srivatsan A, Mohanty A, et al. Cognitive outcomes after unruptured intracranial aneurysm treatment with flow diversion[J]. J Neurosurg, 2019, 134(1): 33-38. doi: 10.3171/2019.9.jns191910 [3] Zdżalik-Bielecka D, Poświata A, Kozik K, et al. The GAS6-AXL signaling pathway triggers actin remodeling that drives membrane ruffling, macropinocytosis, and cancer-cell invasion[J]. Proc Natl Acad Sci USA, 2021, 118(28): e2024596118. doi: 10.1073/pnas.2024596118 [4] Pereira J B, Janelidze S, Strandberg O, et al. Microglial activation protects against accumulation of tau aggregates in nondemented individuals with underlying Alzheimer’s disease pathology[J]. Nat Aging, 2022, 2(12): 1138-1144. doi: 10.1038/s43587-022-00310-z [5] Chen M, Li Z, Da L, et al. LncRNA PVT1 promotes intracranial aneurysm development via USP10/KLF4/NLRP3 axis-mediated pyroptosis in human cerebral smooth muscle cells[J]. J Biochem Mol Toxicol, 2025, 39(1): e70102. doi: 10.1002/jbt.70102 [6] Pilat D, Piotrowska A, Rojewska E, et al. Blockade of IL-18 signaling diminished neuropathic pain and enhanced the efficacy of morphine and buprenorphine[J]. Mol Cell Neurosci, 2016, 71: 114-124. doi: 10.1016/j.mcn.2015.12.013 [7] 谢江涛, 王云莉, 苏永永, 等. 颅内动脉瘤性蛛网膜下腔出血患者术后早期认知功能障碍与铁蛋白表达的相关性研究[J]. 陕西医学杂志, 2017, 46(6): 735-736. doi: 10.3969/j.issn.1000-7377.2017.06.020 [8] 中国医师协会神经介入专业委员会, 中国颅内动脉瘤计划研究组. 颅内动脉瘤影像学判读专家共识[J]. 中国脑血管病杂志, 2021, 18(7): 492-504. [9] 师新娟, 桑春妮, 田英然, 等. 颅内动脉瘤性蛛网膜下腔出血致认知障碍的评估及影响因素[J]. 中华保健医学杂志, 2020, 22(5): 513-515. doi: 10.3969/j.issn.1674-3245.2020.05.018 [10] 中国医师协会神经内科分会认知障碍专业委员会, 《中国血管性认知障碍诊治指南》编写组. 2019年中国血管性认知障碍诊治指南[J]. 中华医学杂志, 2019, 99(35): 2737-2744. [11] Seng L B, Yasuhiro Y, Rajagopal N, et al. Loss of contralateral upper limb motor evoked potential due to occlusion of the internal carotid artery in microsurgical clipping of basilar tip aneurysm[J]. Asian J Neurosurg, 2019, 14(1): 295-299. [12] Martinez-Perez R, Rayo N, Montivero A, et al. The “Brain Stress Timing” phenomenon and other misinterpretations of randomized clinical trial on aneurysmal subarachnoid hemorrhage[J]. Neural Regen Res, 2019, 14(8): 1364-1366. doi: 10.4103/1673-5374.253513 [13] Sakurada K, Ikedo T, Hosokawa Y, et al. Irreversible postoperative cognitive impairment after unruptured intracranial aneurysm treatment in the elderly[J]. Acta Neurochir, 2024, 166(1): 30. doi: 10.1007/s00701-024-05933-2 [14] Wu X B, Luo B, Guo X, et al. Aneurysm wall enhancement and systemic inflammation jointly contribute to cognitive dysfunction in untreated unruptured intracranial aneurysm patients[J]. J Inflamm Res, 2025, 18: 9045-9053. doi: 10.2147/JIR.S515856 [15] Tang Y, Hu H, Xie Q, et al. GAS6/AXL signaling promotes M2 microglia efferocytosis to alleviate neuroinflammation in sepsis-associated encephalopathy[J]. Cell Death Discov, 2025, 11(1): 268. doi: 10.1038/s41420-025-02507-8 [16] 梁国栋, 王伟, 梁景翔. 血清生长停滞特异性蛋白6、含半胱氨酸的天冬氨酸蛋白水解酶1水平与创伤性颅脑损伤患者病情及继发性认知障碍的相关性研究[J]. 创伤与急危重病医学, 2024, 12(5): 290-294. [17] Chang H, An R, Li X, et al. Anti-Axl monoclonal antibodies attenuate the migration of MDA-MB-231 breast cancer cells[J]. Oncol Lett, 2021, 22(5): 749. [18] Lu C, Song Y, Wu X, et al. Pleiotropic role of GAS6 in cardioprotection against ischemia-reperfusion injury[J]. J Adv Res, 2025, 70: 481-497. doi: 10.1016/j.jare.2024.04.020 [19] Miao L, Yu C, Guan G, et al. Extracellular vesicles containing GAS6 protect the liver from ischemia-reperfusion injury by enhancing macrophage efferocytosis via MerTK-ERK-COX2 signaling[J]. Cell Death Discov, 2024, 10(1): 401. doi: 10.1038/s41420-024-02169-y [20] Lei W, Wu S, Zhao A, et al. Psoralidin protects against cerebral hypoxia/reoxygenation injury: Role of GAS6/Axl signaling[J]. Phytother Res, 2022, 36(6): 2628-2640. doi: 10.1002/ptr.7481 [21] Li W, Zhang Z, Li J, et al. Silibinin exerts neuroprotective effects against cerebral hypoxia/reoxygenation injury by activating the GAS6/Axl pathway[J]. Toxicology, 2023, 495: 153598. doi: 10.1016/j.tox.2023.153598 [22] Horie K, Watanabe M, Chanbora C, et al. Bovine lactoferrin reduces extra-territorial facial allodynia/hyperalgesia following a trigeminal nerve injury in the rat[J]. Brain Res, 2017, 1669: 89-96. doi: 10.1016/j.brainres.2017.04.015 [23] Wu D, Li X, Xing Y, et al. The role of IL-18BP in alleviating anxiety-like behaviors after traumatic brain injury in rats by modulating astrocytic pyroptosis in amygdala[J]. Brain Inj, 2025, 39(14): 1348-1356. doi: 10.1080/02699052.2025.2560587 [24] Cheng L, Dong R, Song C, et al. Mediation effects of IL-1β and IL-18 on the association between vitamin D levels and mild cognitive impairment among Chinese older adults: A case-control study in Taiyuan, China[J]. Front Aging Neurosci, 2022, 14: 836311. doi: 10.3389/fnagi.2022.836311 [25] Guan X, Leng W, Hu Q, et al. Association between cognitive function and IL-18 levels in schizophrenia: Dependent on IL18 - 607 A/C polymorphism[J]. Psychoneuroendocrinology, 2023, 158: 106386. doi: 10.1016/j.psyneuen.2023.106386 [26] Li B, Wang L, Xiao Y, et al. Gastrodin ameliorates tau pathology and BBB dysfunction in 3xTg-AD transgenic mice by regulating the ADRA1/NF-κB/NLRP3 pathway to reduce neuroinflammation[J]. Phytother Res, 2025, 39(5): 1996-2016. doi: 10.1002/ptr.8461 [27] Chen Y, Yang C, Zou M, et al. Inhibiting mitochondrial inflammation through Drp1/HK1/NLRP3 pathway: A mechanism of alpinetin attenuated aging-associated cognitive impairment[J]. Phytother Res, 2023, 37(6): 2454-2471. doi: 10.1002/ptr.7767 [28] Kim D H, Lee K J, Park J, et al. Disruption of IL-18 signaling via engineered IL-18BP biologics alleviates experimental cholestatic liver disease[J]. Biomed Pharmacother, 2023, 167: 115587. doi: 10.1016/j.biopha.2023.115587 [29] 李妍, 齐曼曼, 缴宝杰, 等. IL-18结合蛋白在创伤性颅脑损伤大鼠认知功能障碍中的作用及其机制[J]. 解放军医学杂志, 2023, 48(7): 776-783. -
点击查看大图
图(2) / 表(5)
计量
- 文章访问数: 4
- HTML全文浏览量: 5
- PDF下载量: 0
- 被引次数: 0
