[1]钟 曌a,郭继勃b,郭 昊c,等.急性缺血性脑卒中患者血清Kruppel 样转录因子2 水平表达与脑梗死体积及预后的相关性研究[J].现代检验医学杂志,2023,38(06):1-5+12.[doi:10.3969/j.issn.1671-7414.2023.06.001]
 ZHONG Zhaoa,GUO Jibob,GUO Haoc,et al.Correlation between the Level of Serum Kruppel-like Transcription Factor 2 and the Volume of Cerebral Infarction and Prognosis in Patients with Acute Ischemic Stroke[J].Journal of Modern Laboratory Medicine,2023,38(06):1-5+12.[doi:10.3969/j.issn.1671-7414.2023.06.001]
点击复制

急性缺血性脑卒中患者血清Kruppel 样转录因子2 水平表达与脑梗死体积及预后的相关性研究()
分享到:

《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年06期
页码:
1-5+12
栏目:
论著
出版日期:
2023-11-15

文章信息/Info

Title:
Correlation between the Level of Serum Kruppel-like Transcription Factor 2 and the Volume of Cerebral Infarction and Prognosis in Patients with Acute Ischemic Stroke
文章编号:
1671-7414(2023)06-001-06
作者:
钟 曌1a郭继勃1b郭 昊1c韩晓婷2张丽萍1祝 刚1c
(1. 空军军医大学第二附属医院a. 神经内科;b. 急诊科;c. 神经外科,西安 710038;2. 核工业四一七医院神经内科,西安 710699)
Author(s):
ZHONG Zhao1a GUO Jibo1b GUO Hao1c HAN Xiaoting2 ZHANG Liping1 ZHU Gang1c
(1a. Department of Neurology;b. Department of Emergency; c. Department of Neurosurgery, the Second Affiliated Hospital of Air Force Medical University, Xi’an 710038, China; 2. Department of Neurology, Nuclear Industry 417 Hospital, Xi’an 710699, China)
关键词:
急性缺血性卒中Kruppel 样转录因子2脑梗死体积白细胞介素6鞘氨醇激酶1/ 鞘氨醇-1-磷酸
分类号:
R743.33;R392.11
DOI:
10.3969/j.issn.1671-7414.2023.06.001
文献标志码:
A
摘要:
目的 研究急性缺血性脑卒中(acute ischemic stroke,AIS)患者血清Kruppel 样转录因子2(kruppel-like factor 2,KLF2)水平表达与脑梗死体积及预后的关系,探讨KLF2 对AIS 脑梗死体积及预后不良的预测价值,并分析KLF2 诱导AIS 发生的可能机制。方法 收集2021 年4 月~ 2022 年11 月在空军军医大学第二附属医院收治的141 例AIS 患者为研究对象,并收集同期行健康体检者50 例作为对照。根据Pullicino 公式计算AIS 脑梗死体积,分为小梗死灶组、中梗死灶组和大梗死灶组;根据改良Rankin 量表(modified rankin scale,mRS)评分分为预后良好组和预后不良组;采用Pearson 相关性分析血清KLF2 表达与AIS 患者脑梗死体积、预后及白细胞介素6(interleukin-6,IL-6)、鞘氨醇激酶1(sphingosine kinase 1,SphK1)和鞘氨醇-1- 磷酸(sphingosine-1-phosphate,S1P)表达的相关性;绘制ROC 曲线评估血清KLF2 对AIS 预后不良的预测价值。结果 AIS 组患者血清KLF2(194.37±32.37pg/ml)水平显著低于对照组(242.85±17.39pg/ml);IL-6(13.70±2.89pg/ml),S1P(432.58±101.37pg/ml)和SphK1(2.65±0.58pg/ml)水平显著高于对照组(9.92±2.45pg/ml,259.15±78.24pg/ml,1.48±0.36 pg/ml),差异具有统计学意义(t=10.076,-8.253,-10.986,-13.367, 均P < 0.05)。小梗死灶组、中梗死灶组和大梗死灶组血清KLF2 水平分别为217.69±33.14pg/ml,196.48±29.53pg/ml 和168.94±31.62pg/ml,差异有统计学意义(F=25.753,P<0.001)。AIS 预后良好组血清KLF2 水平为211.83±28.46pg/ml,明显高于预后不良组的170.12±25.34pg/ml,差异有统计学意义(t=8.982,P<0.001)。血清KLF2 水平与AIS 脑梗死体积、预后及IL-6,SphK1 水平呈负相关性(r=-0.607,-0.586,-0.480,-0.522,均P<0.05), 与S1P 水平无明显相关性(r=0.172,P>0.05); 血清SphK1 与S1P 水平呈明显正相关(r=0.480,P<0.05)。血清KLF2 预测AIS 脑梗死体积(中~大梗死灶)和预后不良的AUC 值分别为0.871 和0.889,当截断值分别取206.1 pg/ml 和192.37 pg/ml 时,诊断灵敏度和特异度较高。结论 AIS 血清中KLF2 表达降低与患者脑梗死体积及预后关系密切,可作为AIS 病情评估及判断预后不良的有效生物指标。血清KLF2 表达与IL-6,SphK1 水平存在明显相关性,KLF2 可能调控SphK1/S1P 途径参与神经炎症反应,介导AIS 发生、发展,为临床研究及治疗提供了新的靶标。
Abstract:
Objective To investigate the relationship between serum Kruppel-like transcription factor 2 (KLF2) expression and cerebral infarction volume and prognosis in patients with acute ischemic stroke (AIS), explore the predictive value of KLF2 for poor prognosis of AIS, and analyze the possible mechanism of KLF2 in the occurrence of AIS. Methods A total of 141 AIS patients admitted to the Second Affiliated Hospital of the Air Force Military Medical University from April 2021 to November 2022 were collected for the study, and collected 50 healthy individuals who underwent physical examinations during the same period as controls. According to the Pullicino formula, the volume of AIS cerebral infarction was calculated and divided into small infarction group, medium infarction group, and large infarction group. A Pearson correlation analysis was conducted between serum KLF2 expression and cerebral infarct volume, prognosis, interleukin (IL) -6, sphingosine kinase 1 (SphK1)and sphingosine-1-phosphate (S1P) expression AIS patients. Draw ROC curve to evaluate the predictive value of serum KLF2 for poor prognosis of AIS. Results The serum KLF2(194.37±32.37pg/ml)levels of AIS patients were significantly lower than those of the control group(242.85±17.39pg/ml), while the levels of IL-6(13.70±2.89pg/ml), S1P(432.58±101.37pg/ml), and SphK1(2.65±0.58pg/ml) were significantly higher than those of the control group(9.92±2.45pg/ml, 259.15±78.24pg/ml, 1.48±0.36 pg/ml), with statistically significant differences (t=10.076, -8.253, -10.986, -13.367,all P<0.05). The serum KLF2 levels in the small infarction group, the medium infarction group and the large infarction group were 217.69±33.14pg/ml, 196.48±29.53pg/ml and 168.94±31.62pg/ml, respectively, and the difference was statistically significant (F=25.753, P<0.001). Serum KLF2 level in AIS group with good prognosis was 211.83±28.46pg/ml, which was significantly higher than that in group with poor prognosis 170.12±25.34pg/ml, and the difference was statistically significant (t=8.982,P<0.001).The serum KLF2 level was negatively correlated with AIS cerebral infarction volume, prognosis, IL-6, and SphK1 levels (r= -0.607, -0.586, -0.480, -0.522,all P<0.05), but there was no significant correlation with S1P level (r=0.172, P>0.05). There was a significant positive correlation between serum SphK1 and S1P levels (r=0.480, P<0.05). The AUC values of serum KLF2 for predicting AIS infarct volume (medium to large infarct) and poor prognosis were 0.871 and 0.889, respectively. When cut-off values were 206.1 pg/ml and 192.37 pg/ml, the diagnostic sensitivity and specificity were higher. Conclusion The decreased expression of KLF2 in AIS serum was closely related to the cerebral infarction volume and prognosis of patients, and can be used as an effective biological indicator for the assessment of AIS disease and the judgment of poor prognosis. Serum KLF2 expression was significantly correlated with the levels of IL-6 and SphK1. KLF2 may regulate the SphK1/S1P pathway to participate in neuroinflammatory response and mediate the occurrence and development of AIS, providing a new target for clinical research and treatment.

参考文献/References:

[1] MENDELSON S J, PRABHAKARAN S. Diagnosis and management of transient ischemic attack and acute ischemic stroke: a review[J]. Journal of the American Medical Association, 2021, 325(11): 1088-1098.
[2] 杜仁峰, 余波, 潘丹红, 等.缺血性脑卒中血脑屏障受损及修复的神经炎性机制研究进展[J].华西医学,2022, 37(4): 622-626. DU Renfeng, YU Bo, PAN Danhong, et al. Research progress on neuroinflammatory mechanism of bloodbrain barrier damage and repair in ischemic stroke[J].West China Medical Journal, 2022, 37(4): 622-626.
[3] TANG Xinmiao, WANG Peiwei, ZHANG Rongli, et al. KLF2 regulates neutrophil activation and thrombosis in cardiac hypertrophy and heart failure progression[J].Journal of Clinical Investigation, 2022, 132(3): e147191.
[4] TURPAEV K T. Transcription factor KLF2 and its role in the regulation of inflammatory processes[J].Biochemistry. (Mosc), 2020, 85(1): 54-67.
[5] 闫欣, 商素亮, 李娜, 等. 血浆S1P 和HDL-C 表达水平与帕金森病患者临床症状的相关性研究[J]. 现代检验医学杂志, 2022, 37(3): 182-186, 190. YAN Xin, SHANG Suliang, LI Na, et al. Correlation between plasma S1P, HDL-C expressions levels and clinical symptoms in patients with Parkinson’s disease[J]. Journal of Modern Laboratory Medicine,2022, 37(3): 182-186, 190.
[6] QIANG Guanghui, WANG Zhongxia, JI Anlai, et al. Sphingosine kinase 1 knockout alleviates hepatic ischemia/reperfusion injury by attenuating inflammation and oxidative stress in mice[J]. Hepatobiliary & Pancreatic Diseases International, 2019, 18(3): 255-265.
[7] ZHU Xuan, WANG Xinlin, YING Tianhao, et al. Kaempferol alleviates the inflammatory response and stabilizes the pulmonary vascular endothelial barrier in LPS-induced sepsis through regulating the SphK1/S1P signaling pathway [J]. Chem Biol Interact, 2022,368:110221.
[8] 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. 中国急性缺血性脑卒中诊治指南2018[J]. 中华神经科杂志, 2018, 51(9): 666-682. Chinese Society of Neurology, Chinese Stroke Society. Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018 [J]. Chinese Journal of Neurology,2018, 51(9): 666-682.
[9] 张本银, 路吾长, 杨靖.美国国立卫生研究院卒中量表评分、血浆同型半胱氨酸水平与急性脑梗死的关系及危险因素分析[J].实用临床医药杂志, 2021,25(22): 102-105. ZHANG Benyin, LU Wuchang, YANG Jing. Relationships of National Institutes of Health Stroke Scale score, plasma homocysteine level with acute cerebral infarction and analysis in related risk factors[J]. Journal of Clinical Medicine in Practice, 2021, 25(22): 102-105.
[10] HAGGAG H, HODGSON C. Clinimetrics: modified rankin scale (mRS)[J]. Journal of Physiotherapy, 2022,68(4): 281.
[11] GORELICK P B. The global burden of stroke:persistent and disabling[J]. Lancet Neurolog, 2019,18(5): 417-418.
[12] JURCAU A, SIMION A. Neuroinflammation in cerebral ischemia and ischemia/reperfusion injuries:from pathophysiology to therapeutic strategies[J].International Journal of Molecular Sciences, 2021,23(1): 14.
[13] LI Qiqi, LI Jiaying, ZHOU Ming, et al. Targeting neuroinflammation to treat cerebral ischemia -the role of TIGAR/NADPH axis[J]. Neurochemistry International, 2021, 148: 105081.
[14] 黄欣欣, 应燕萍.Kruppel 样因子2 与心血管疾病的研究进展[J]. 中国比较医学杂志, 2022, 32(2): 94-98,132. HUANG Xinxin, YING Yanping. Research progress of Kruppel-like factor 2 and cardiovascular diseases[J].Chinese Journal of Comparative Medicine, 2022, 32(2):94-98, 132.
[15] TIAN Rui, LI Ranran, LIU Yiyun, et al. Metformin ameliorates endotoxemiainduced endothelial proinflammatory responses via AMPK-dependent mediation of HDAC5 and KLF2[J]. Biochim Biophys Acta Mol Basis Dis, 2019, 1865(6): 1701-1712.
[16] WU Weidang, GENG Pengbo, ZHU Jun, et al. KLF2 regulates eNOS uncoupling via Nrf2/HO-1 in endothelial cells under hypoxia and reoxygenation[J].Chemico-Biological Interactions, 2019, 305: 105-111.
[17] JHA P, DAS H. KLF2 in regulation of NF-κBmediated immune cell function and inflammation[J].International Journal of Molecular Sciences, 2017,18(11): 2383.
[18] ZHANG Benping, LI Jiebing.Phoenixin-14 protects human brain vascular endothelial cells against oxygenglucose deprivation/reoxygenation (OGD/R)-induced inflammation and permeability[J]. Archives of Biochemistry and Biophysics, 2020, 682: 108275.
[19] VILA E, SOL? M, MASIP N, et al. Uric acid treatment after stroke modulates the Krüppel-like factor 2-VEGF-A axis to protect brain endothelial cell functions: impact of hypertension [J]. Biochem Pharmacol, 2019, 164: 115-128.
[20] 金会, 许秋琳, 翁伟力, 等.急性脑梗死患者血清锌指样转录因子2、脂蛋白相关磷脂酶A2 水平及其与病情相关性研究[J].临床军医杂志, 2020, 48(1):93-94, 96. JIN Hui, XU Qiulin, WENG Weili, et al. Study on serum Zinc finger-like transcription factor 2 and lipoprotein-associated phospholipase A2 levels in patients with acute cerebral infarction[J]. Clinical Journal of Medical Officers, 2020, 48(1): 93-94, 96.
[21] 黎红华, 盛冲霄.亲环素A 和Krüppel 样转录因子2 及内皮型一氧化氮合酶在大鼠动脉粥样硬化病变过程中的表达变化[J].中国脑血管病杂志, 2015,12(5): 245-249. LI Honghua, SHENG Chongxiao. Expression changes of cyclophilin A, Krüppel-like factor 2,and endothelial nitric oxide synthase in the pathological process of atherosclerosis in rats[J]. Chinese Journal of Cerebrovascular Diseases, 2015, 12(5): 245-249.
[22] YAMAMOTO S, YAKO Y, FUJIOKA Y, et al. A role of the sphingosine-1-phosphate(S1P)-S1P receptor2 pathway in epithelial defense against cancer(EDAC)[J].Molecular Biology of the Cell, 2016, 27(3): 491-499.
[23] SU Danying, CHENG Yuefeng, LI Shi, et al. Sphk1 mediates neuroinflammation and neuronal injury via TRAF2/NF-κB pathways in activated microglia in cerebral ischemia reperfusion [J].Journal of Neuroimmunology, 2017, 305: 35-41.
[24] ZHENG Zhi, ZENG Yongzhi, REN Kun, et al. S1P promotes inflammation-induced tube formation by HLECs via the S1PR1/NF-κB pathway [J].International Immunopharmacology, 2019, 66: 224-235.
[25] JIN Liming, LIU Yuanxing, CHENG Jian, et al. The effect of SphK1/S1P signaling pathway on hepatic sinus microcirculation in rats with hepatic ischemiareperfusion injury[J]. Hepatobiliary & Pancreatic Diseases International , 2022, 21(1): 94-98.
[26] 王晓楠, 周叶, 于晓红, 等.瑞舒伐他汀对ox-LDL诱导的内皮细胞损伤中SphK1/S1P/NF-κB 信号通路的影响[J]. 中国老年学杂志, 2017, 37(8): 1897-1899. WANG Xiaonan, ZHOU Ye, YU Xiaohong, et al. Effect of rosuvastatin on SphK1/S1P/NF-κB signaling pathway in Ox-LDL-induced endothelial cell injury[J].Chinese Journal of Gerontology, 2017, 37(8): 1897-1899.

相似文献/References:

[1]董汉宁a,彭芸娟a,雷国奇b,等.急性缺血性脑卒中患者血清sTREM2 和DKK-1 水平检测对抑郁发生的预测价值研究[J].现代检验医学杂志,2023,38(06):136.[doi:10.3969/j.issn.1671-7414.2023.06.025]
 DONG Hanninga,PENG Yunjuana,LEI Guoqib,et al.Predictive Value of Serum sTREM2 and DKK-1 Levels in Patients with Acute Ischemic Stroke for the Occurrence of Depression[J].Journal of Modern Laboratory Medicine,2023,38(06):136.[doi:10.3969/j.issn.1671-7414.2023.06.025]
[2]沈丹丹,王 鸿.溃疡性结肠炎活动期患者血清TRIM22 和KLF2 水平与病情及临床结局的关系[J].现代检验医学杂志,2024,39(04):143.[doi:10.3969/j.issn.1671-7414.2024.04.026]
 SHEN Dandan,WANG Hong.Relationship among Serum TRIM22 and KLF2 Levels, Disease Condition and Clinical Outcome of Patients with Active Ulcerative Colitis[J].Journal of Modern Laboratory Medicine,2024,39(06):143.[doi:10.3969/j.issn.1671-7414.2024.04.026]

备注/Memo

备注/Memo:
基金项目: 国家自然科学基金(项目批准号:81903072):外泌体miRNA-1246 调控内质网应激凋亡通路在胶质母细胞瘤化疗耐药中的作用和机制研究。
作者简介:钟曌(1983-),女,本科,主治医师,神经内科,研究方向:脑卒中、癫痫、帕金森,E-mail:h6n2gb8@163.com。
通讯作者:郭继勃(1989-),男,主治医师,急诊科,E-mail:1030362483@qq.com.。
更新日期/Last Update: 2023-11-15