Expression of serum SUR1 in middle-aged and elderly patients with aneurysmal subarachnoid hemorrhage and its relationship with prognosis
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摘要:
目的 探讨中老年动脉瘤性蛛网膜下腔出血(aSAH)患者血清磺脲类受体1(SUR1)表达及其与预后的相关性。 方法 选取宁波市第六医院2015年7月—2019年5月收治的91例aSAH患者为观察对象,采用荧光实时定量聚合酶链反应(qRT-PCR)检测术前血清SUR1表达,将所有患者依据术前血清SUR1表达中位数分为SUR1低表达组(46例)、SUR1高表达组(45例);术前采用美国国立卫生研究院卒中量表(NIHSS)评分评估aSAH患者神经缺损程度,术后6个月采用格拉斯哥预后评分(GOS)评估预后,将患者分为预后良好组(77例)、预后不良组(14例)。比较预后良好组与预后不良组术前血清SUR1表达;采用Spearman分析患者血清SUR1表达与NIHSS评分相关性;采用COX模型分析aSAH患者预后影响因素。 结果 预后良好组高血压史患者比例、糖尿病史患者比例、术前NIHSS评分、手术时机均低于预后不良组(均P < 0.05);与预后良好组相比,预后不良组aSAH患者血清SUR1表达较高(P < 0.05);Spearman相关分析显示,aSAH患者血清SUR1表达与NIHSS评分呈正相关(P < 0.05);COX回归模型分析结果显示,年龄 > 60岁、有高血压史、有糖尿病史、NIHSS评分≥15分、手术时机3~7 d、SUR1高表达均是aSAH患者预后的独立危险因素(均P < 0.05)。 结论 SUR1可能参与中老年aSAH的发生及病情演变,有可能成为评估aSAH病情的血清学指标及治疗靶点。 -
关键词:
- 中老年 /
- 动脉瘤性蛛网膜下腔出血 /
- 磺脲类受体1 /
- 预后
Abstract:Objective To investigate the expression and correlation of serum sulfonylurea receptor 1 (SUR1) in middle-aged and elderly patients with aneurysmal subarachnoid haemorrhage (aSAH). Methods Ninety-one patients suffering from aSAH admitted to Ningbo Sixth Hospital from July 2015 to May 2019 were selected as the observation objects. The expression of SUR1 in serum before operation was detected via fluorescence real-time quantitative polymerase chain reaction. According to the median expression of Sulfonylurea receptor 1(SUR1) in serum before operation, the patients were divided into low SUR1 expression group (n=46) and high SUR1 expression group (n=45). Before operation, the degree of nerve defect in the patients with aSAH was evaluated using the national institutes of health stroke scale (NIHSS) score. At 6 months after operation, prognosis was assessed using the Glasgow Outcome Scale, and the patients were divided into good prognosis group (n=77) and poor prognosis group (n=14). The expression of SUR1 before operation was compared between the two groups. The correlation between SUR1 expression and NIHSS score was evaluated via Spearman correlation analysis. The prognostic factors of the patients with aSAH were analysed via Cox model. Results The proportion of patients with hypertension history, with diabetes history, preoperative NIHSS score and operative timing in the good prognosis group were lower than those in the poor prognosis group (all P < 0.05). The expression of serum SUR1 in patients with aSAH in the poor prognosis group was higher than that in the good prognosis group (P < 0.05). Spearman correlation analysis revealed a positive correlation between serum SUR1 expression and NIHSS score in the patients with aSAH (P < 0.05). The Results of Cox regression model showed that age of >60 years, history of hypertension, history of diabetes, NIHSS score ≥15, 3-7 d of operation timing and SUR1 overexpression were all independent risk factors for the prognosis of patients with aSAH (all P < 0.05). Conclusion SUR1 may be involved in the development and progression of aSAH in the middle-aged and the elderly, and may become a serological index for the assessment of aSAH and treatment target. -
表 1 2组aSAH患者一般资料比较[例(%)]
组别 例数 性别(男/女, 例) 年龄(x±s, 岁) 高血压史 糖尿病史 饮酒史 高脂血症史 术前NIHSS评分(x±s, 分) 手术时机(x±s, d) 预后良好组 77 50/27 63.29±7.25 19(24.68) 6(7.79) 10(12.99) 12(15.58) 13.62±3.59 3.53±0.85 预后不良组 14 8/6 64.03±6.61 8(57.14) 5(35.71) 3(21.43) 2(14.29) 17.18±4.33 5.29±1.36 统计量 0.311a 0.356b 5.984a 8.691a 0.172a 0.078a 3.305b 6.431b P值 0.577 0.723 0.014 0.003 0.678 0.780 0.001 < 0.001 注:a为χ2值,b为t值。 表 2 aSAH患者预后危险因素的单因素分析
项目 B SE Wald χ2 P值 OR值 95% CI 年龄 0.891 0.289 9.500 0.002 2.437 1.651~3.598 高血压史 0.826 0.253 10.666 0.001 2.284 1.391~3.749 糖尿病史 0.787 0.223 12.458 < 0.001 2.197 1.133~4.262 NIHSS评分 0.979 0.271 13.063 < 0.001 2.663 1.582~4.483 手术时机 0.623 0.212 8.643 0.003 1.865 1.568~2.219 SUR1表达 0.886 0.308 8.272 0.004 2.425 1.603~3.668 表 3 aSAH患者预后危险因素的多因素分析
项目 B SE Wald χ2 P值 OR值 95% CI 年龄 0.708 0.221 10.250 0.001 2.029 1.427~2.885 高血压史 0.763 0.242 9.932 0.002 2.144 1.339~3.434 糖尿病史 0.703 0.201 12.236 < 0.001 2.020 1.061~3.844 NIHSS评分 0.750 0.247 9.220 0.002 2.117 1.293~3.466 手术时机 0.486 0.155 9.811 0.002 1.625 1.262~2.093 SUR1表达 0.798 0.168 22.535 < 0.001 2.220 1.597~3.086 -
[1] 中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国蛛网膜下腔出血诊治指南2015[J]. 中华神经科杂志, 2016, 49(3): 182-191. doi: 10.3760/cma.j.issn.1006-7876.2016.03.003 [2] WAN Y, HUA Y, GARTON H J L, et al. Activation of epiplexus macrophages in hydrocephalus caused by subarachnoid hemorrhage and thrombin[J]. CNS Neurosci Ther, 2019, 25(4): 1134-1141. doi: 10.1111/cns.13203 [3] 何士科. 介入栓塞术与颅内夹闭术治疗高分级动脉瘤性蛛网膜下腔出血的临床分析[J]. 中华全科医学, 2017, 15(6): 974-976. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY201706021.htm [4] WU J X, DING D, WANG M, et al. Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels[J]. Protein Cell, 2018, 9(6): 553-567. doi: 10.1007/s13238-018-0530-y [5] YANG Y Y, LONG R K, FERRARA C T, et al. A new familial form of a late-onset, persistent hyperinsulinemic hypoglycemia of infancy caused by a novel mutation in KCNJ11[J]. Channels, 2017, 11(6): 636-647. doi: 10.1080/19336950.2017.1393131 [6] SON Y, KIM K, CHO H R, et al. Sildenafil protects neuronal cells from mitochondrial toxicity induced by β-amyloid peptide via ATP-sensitive K+ channels[J]. Biochem Biophys Res Commun, 2018, 500(2): 504-510. doi: 10.1016/j.bbrc.2018.04.128 [7] BHARDWAJ A, KUMAR S, SHARMA A, et al. Advanced age and higher National Institutes of Health Stroke Scale score as predictors of poor outcome in ischemic stroke patients treated with alteplase: a study from a tertiary care centre in rural north-west India[J]. J Neurosci Rural Pract, 2017, 8(2): 236-240. doi: 10.4103/jnrp.jnrp_431_16 [8] AZURMENDI L, DEGOS V, TIBERTI N, et al. Neopterin plasma concentrations in patients with aneurysmal subarachnoid hemorrhage: correlation with infection and long-term outcome[J]. J Neurosurg, 2016, 124(5): 1287-1299. doi: 10.3171/2015.3.JNS142212 [9] 李刚, 赵东刚, 陈少军, 等. 动脉瘤性蛛网膜下腔出血合并脑室出血患者早期神经功能恶化的影响因素[J]. 山东医药, 2017, 57(4): 64-66. doi: 10.3969/j.issn.1002-266X.2017.04.021 [10] DAOU B J, KODURI S, THOMPSON B G, et al. Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage[J]. Cns Neurosci Ther, 2019, 25(10): 1096-1112. doi: 10.1111/cns.13222 [11] 陈郭哲, 常薪霞, 夏明锋, 等. 不同病程2型糖尿病伴脂肪肝患者代谢参数与胰岛功能的相关性分析[J]. 中国临床医学, 2018, 25(1): 65-69. https://www.cnki.com.cn/Article/CJFDTOTAL-LCYX201801016.htm [12] 高政南. 磺脲类药物在2型糖尿病长期血糖管理中的应用[J]. 中华糖尿病杂志, 2018, 10(3): 237-240. doi: 10.3760/cma.j.issn.1674-5809.2018.03.016 [13] 张娅男, 侯景栋, 张宝娟, 等. 丙泊酚对大鼠脑缺血-再灌注损伤时含Kir6.2和SUR1亚基的线粒体ATP敏感性钾通道的影响[J]. 临床麻醉学杂志, 2016, 32(3): 288-290. https://www.cnki.com.cn/Article/CJFDTOTAL-LCMZ201603027.htm [14] LEECH C A, KOPP R F, NELSON H A, et al. Stromal interaction molecule 1 (STIM1) regulates ATP-sensitive potassium (KATP) and store-operated Ca2+ channels in MIN6 β-cells[J]. J Biol Chem, 2017, 292(6): 2266-2277. doi: 10.1074/jbc.M116.767681 [15] 李宏玉, 唐强, 朱路文, 等. 运动预处理对脑缺血再灌注大鼠线粒体ATP敏感性钾通道蛋白及细胞凋亡的影响[J]. 中国康复理论与实践, 2018, 24(5): 497-501. doi: 10.3969/j.issn.1006-9771.2018.05.001 [16] 张致苍, 杨慧平, 李培杰. 格列本脲对急性一氧化碳中毒大鼠脑损伤保护的实验研究[J]. 中国急救复苏与灾害医学杂志, 2018, 13(6): 553-556. doi: 10.3969/j.issn.1673-6966.2018.06.018 [17] STIENEN M N, GERMANS M, BURKHARDT J K, et al. Predictors of in-hospital death after aneurysmal subarachnoid hemorrhage: analysis of a nationwide database (Swiss SOS [Swiss Study on Aneurysmal Subarachnoid Hemorrhage])[J]. Stroke, 2018, 49(2): 333-340. doi: 10.1161/STROKEAHA.117.019328 [18] 何士科. 介入栓塞术与颅内夹闭术治疗高分级动脉瘤性蛛网膜下腔出血的临床分析[J]. 中华全科医学, 2017, 15(6): 974-976. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY201706021.htm [19] NG I, DU R. Thirty-day readmissions in aneurysmal subarachnoid hemorrhage: a good metric for hospital quality?[J]. J Neurosci Res, 2020, 98(1): 219-226. doi: 10.1002/jnr.24398 [20] 张伟平, 屈洪党. 蛛网膜下腔出血的诊断与治疗[J]. 中华全科医学, 2019, 17(3): 345-346. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY201903002.htm [21] 邱方方, 陆远强. 影响动脉瘤性蛛网膜下腔出血的预后因素分析[J]. 中华急诊医学杂志, 2019, 28(3): 379-383. https://www.cnki.com.cn/Article/CJFDTOTAL-NXGB201906002.htm [22] 余金辉, 朱继, 何朝晖, 等. 高分级动脉瘤性蛛网膜下腔出血手术治疗患者预后不良的影响因素分析[J]. 中国脑血管病杂志, 2019, 16(6): 288-295. doi: 10.3969/j.issn.1672-5921.2019.06.002