[1]李长宝,刘 磊,宋保新,等.自发性脑出血患者血清miR-143 和HMGA2 表达水平与预后的预测价值研究[J].现代检验医学杂志,2023,38(02):69-74.[doi:10.3969/j.issn.1671-7414.2023.02.013 ]
　LI Chang-bao,LIU Lei,SONG Bao-xin,et al.Predictive Value of Serum miR-143 and HMGA2 Expression Levels and Prognosis in Patients with Spontaneous Intracerebral Hemorrhage[J].Journal of Modern Laboratory Medicine,2023,38(02):69-74.[doi:10.3969/j.issn.1671-7414.2023.02.013 ]
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自发性脑出血患者血清miR-143 和HMGA2 表达水平与预后的预测价值研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年02期
页码:
69-74
栏目:
论著
出版日期:
2023-03-15

文章信息/Info

Title:
Predictive Value of Serum miR-143 and HMGA2 Expression Levels and Prognosis in Patients with Spontaneous Intracerebral Hemorrhage
文章编号:
1671-7414（2023）02-069-06
作者:
李长宝1; 刘 磊2; 宋保新1; 沈俊岩1; 张云鹏1
（1.首都医科大学附属北京友谊医院平谷医院神经外科，北京 101200；2.解放军总医院第一医学中心神经外科，北京 100853）
Author(s):
LI Chang-bao1;  LIU Lei2;  SONG Bao-xin1;  SHEN Jun-yan1;  ZHANG Yun-peng1
（1. Department of Neurosurgery, Pinggu Hospital of Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing 101200，China；2. Department of Neurosurgery, the first Medical Center of PLA General Hospital, Beijing 100853，China）
关键词:
自发性脑出血; 微小核糖核酸 -143; 高迁移率族蛋白 A2
分类号:
R743.34；R392.11
DOI:
10.3969/j.issn.1671-7414.2023.02.013
文献标志码:
A
摘要:
目的 分析自发性脑出血 (spontaneous intracerebral hemorrhage， sICH)患者血清微小核糖核酸（microRNA， miR）-143，高迁移率族蛋白 A2（high mobility group protein A2 ，HMGA2）的水平及其与预后的关系。方法 选取 2020年 8月～2022年 6月首都医科大学附属北京友谊医院平谷医院收治的 129例 sICH患者作为 sICH组，根据 sICH患者脑出血体积分为小血肿组 50例（n=50，<10 ml）、中血肿组（n=45，10~30 ml）和大血肿组（n=34，>30 ml）；根据 sICH患者住院 30天内是否死亡，将患者分为死亡组（n=40，预后不良）和存活组（n=89，预后良好），另选取同期来医院体检的 131例健康者作为对照组。收集受试者临床资料，分别采用荧光定量 PCR法和酶联免疫吸附法检测 sICH患者入院 24 h内、健康者体检时血清 miR-143和 HMGA2水平；分析 sICH患者血清 miR-143和 HMGA2水平与美国国立卫生研究院卒中量表（NIHSS）、格拉斯哥昏迷量表 (GCS)、Rankin量表 (mRS)评分间的相关性， miR-143和 HMGA2对 sICH患者预后不良的预测价值以及影响 sICH患者预后不良的危险因素。结果 与对照组比较， sICH组血清 miR-143水平（0.35±0.10 vs 1.03±0.07）降低， HMGA2水平（266.97±79.38mg/ml vs 153.13±40.24mg/ml）升高，差异具有统计学意义（t=63.599，14.618，均 P<0.001）。小血肿组、中血肿组和大血肿组 sICH患者血清 miR-143水平（0.38±0.11，0.34±0.10，0.27±0.09）依次降低， HMGA2水平（212.01±78.72mg/ml，251.62±79.31mg/ml， 368.11±80.44mg/ml）依次升高，差异具有统计学意义（F=11.895，40.424，均 P<0.001）。与存活组比较，死亡组患者血清 miR-143水平（0.30±0.06 vs 0.37±0.12）降低， HMGA2水平（316.81±80.03mg/ml vs 244.57±79.09mg/ml）升高，差异具有统计学意义（t=3.493，4.781，均 P<0.05）。sICH患者血清 miR-143水平与 NIHSS，mRS评分呈负相关（r=-0.423，-0.498，均 P<0.001），与 GCS评分呈正相关（r=0.546，P<0.001）。HMGA2水平与 NIHSS，mRS评分呈正相关（r=0.875，0.863，均 P<0.001），与 GCS评分呈负相关（r=-0.659，P<0.001）。血清 miR-143，HMGA2及二者联合预测 sICH患者预后不良的曲线下面积分别为 0.733，0.811，0.856，NIHSS评分高 [OR（95%CI）=1.968（1.108~3.495）]、 GCS评分低 [OR（95%CI）=1.923（1.043~3.545）]、mRS评分高 [OR（95%CI）=2.130（1.204~3.768）]、血清 miR-143水平低 [OR（95%CI）=2.013（1.120~3.617）]和 HMGA2水平高 [OR（95%CI）=2.330（1.325~4.097）]是 sICH患者预后不良的危险因素（均 P<0.05）。结论 sICH患者血清 miR-143和 HMGA2异常表达与患者出血体积及预后有关，可作为 sICH患者病情评估和预后评估的辅助指标。
Abstract:
Objective To analyze the levels of serum micro RNA (miR) -143 and high mobility group protein A2 (HMGA2) in patients with spontaneous intracerebral hemorrhage (sICH) and their relationship with prognosis. Methods A total of 129 sICH patients admitted to Pinggu Hospital of Beijing Friendship Hospital Affiliated to Capital Medical University during August 2020 to June 2022 were included as the sICH group. According to the volume of intracerebral hemorrhage of sICH patients, they were divided into 50 of small hematoma group (n=50, <10 ml), medium hematoma group (n=45, 10~30 ml), and large hematoma group (n=34, >30 ml). According to whether sICH patients died within 30 days of hospitalization, the patients were divided into death group (n=40, poor prognosis) and survival group (n=89, good prognosis). In addition, 131 healthy people who came to the hospital for physical examination during the same period were selected as the control group. Clinical data of the subjects were collected. fluorescence quantitative PCR and enzyme-linked immunosorbent assay were used to detect the serum levels of miR-143 and HMGA2 in sICH patients within 24 hours after admission and healthy subjects during physical examination. Analyze the correlation between serum miR-143 and HMGA2 levels and NIHSS, GCS and mRS scores in sICH patients, the predictive value of miR-143 and HMGA2 in poor prognosis of sICH patients and the risk factors affecting poor prognosis of sICH patients. Results Compared with the control group, the serum miR-143 level (0.35±0.10 vs 1.03±0.07) in sICH group was decreased, and the serum HMGA2 level (266.97±79.38mg/ml vs 153.13±40.24mg/ml) was increased, the differences were statistically significant (t=63.599, 14.618, all P<0.001). The serum miR-143 level (0.38±0.11, 0.34±0.10, 0.27±0.09) of sICH patients in small hematoma group, medium hematoma group and large hematoma group was successively decreased, and the serum HMGA2 level (212.01±78.72mg/ml, 251.62±79.31mg/ml, 368.11±80.44mg/ml) was successively increased, and the differences were statistically significant (F=11.895, 40.424, all P<0.001).Compared with survival group, the serum miR-143 level (0.30±0.06 vs 0.37±0.12) in death group was decreased, and the serum HMGA2 level (316.81±80.03mg/ml vs 244.57±79.09mg/ml) was increased, and the difference was statistically significant (t=3.493, 4.781, all P<0.05).Serum miR-143 level in sICH patients was negatively correlated with NIHSS and mRS score (r=-0.423, -0.498, all P<0.001), and positively correlated with GCS score (r=0.546, P<0.001).HMGA2 level was positively correlated with NIHSS and mRS score (r=0.875, 0.863, all P<0.001), and negatively correlated with GCS score (r=-0.659, P<0.001). The areas under curve of serum miR-143, HMGA2 and their combination in predicting poor prognosis of sICH patients were 0.733, 0.811 and 0.856, respectively. High NIHSS score [OR(95%CI)=1.968(1.108~3.495)], low GCS score [OR(95%CI)=1.923(1.043~3.545)], high mRS score [OR(95%CI)=2.130(1.204~3.768)], low serum miR-143 level [OR(95%CI)=2.013(1.120~3.617)] and high HMGA2 level [OR(95%CI)=2.330(1.325~4.097)] were risk factors for poor prognosis in sICH patients (all P<0.05). Conclusion The abnormal expression of serum miR-143 and HMGA2 in patients with sICH was related to the bleeding volume and prognosis of patients, and they can be used as auxiliary indicators for the evaluation of the condition and prognosis of patients with sICH.

参考文献/References:

[1] DULOQUIN G, GRABER M, BAPTISTE L, et al. Acute management of spontaneous intracerebral hemorrhage[J].Rev Med Interne, 2022, 43(5):293-300.
[2] 苏龙 , 车海江 , 林涛 ,等 . 脑出血患者血清神经丝轻链水平与病情程度及早期预后的相关性研究 [J].现代检验医学杂志 , 2021, 36(4):101-105. SU Long, CHE Haijiang, LIN Tao, et al. Correlation of serum neurofilament light chain and severity and early prognosis in patients with acute intracerebral hemorrhage [J]. Journal of Modern Laboratory Medicine, 2021, 36(4):101-105.
[3] GUO Xin, ZHONG Rui, HAN Yujuan, et al. Incidence and relevant factors for seizures after spontaneous intracerebral hemorrhage: A systematic review and meta-analysis[J]. Seizure, 2022, 101:30-38.
[4] 陈欣 , 周丽华 , 郭媛博 ,等 . 急性自发性脑出血患者血清指标与脑水肿体积及预后相关性研究 [J]. 创伤与急危重病医学 , 2020, 8(4): 294-297,300. CHEN Xin, ZHOU Lihua, GUO Yuanbo, et al. Correlation between serum indexes and cerebral edema volume and prognosis in patients with acute spontaneous intracerebral hemorrhage[J]. Trauma and Critical Care Medicine, 2020, 8(4): 294-297,300.
[5] MüLLER M, TAPIA-PEREZ J H, YILDIZ C, et al. Alterations in inflammatory markers and clinical outcome after spontaneous intracerebral hemorrhage - preliminary results [J]. J Stroke Cerebrovasc Dis, 2020, 29(8):104861.
[6] 栗春梅 , 俞晓飞 . 高迁移率族蛋白 B1在脑出血炎症损伤和修复中的作用研究进展 [J]. 中西医结合心脑血管病杂志 , 2020, 18(13): 2075-2078. LI Chunmei, YU Xiaofei. Research progress on the role of high mobility group protein B1 in inflammatory injury and repair of intracerebral hemorrhage[J]. Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease, 2020, 18(13): 2075-2078.
[7] SILENO S, BEJI S, D’AGOSTINO M, et al. MicroR-NAs involved in psoriasis and cardiovascular diseas-es[J]. Vasc Biol,2021 ,3(1):R49-R68.
[8] IWUCHUKWU I , NGUYEN D , BEAVERS M , et al. MicroRNA regulatory network as biomarkers of late seizure in patients with spontaneous intracerebral hemorrhage[J]. Molecular Neurobiology, 2020, 57(5):2346-2357.
[9] SUN J D, LI X M, LIU J L, et al. Effects of miR-150-5p on cerebral infarction rats by regulating the Wnt signaling pathway via p53 [J]. Eur Rev Med Pharmacol Sci, 2020, 24(7):3882-3891.
[10] GAO Ge, ZHANG Yang, YU Jian, et al. Long non-coding RNA MALAT1/microRNA-143/VEGFA signal axis modulates vascular endothelial injury-induced intracranial aneurysm [J]. Nanoscale Res Lett, 2020, 15(1): 139.
[11] 喇慧 , 权丽丽 , 张玉琼 . 血清高迁移率族蛋白 A2、糖类抗原 125、人附睾蛋白 4在卵巢上皮癌中的表达及诊断价值分析 [J].癌症进展 , 2021, 19(18): 1871-1873，1881. LA Hui, QUAN Lili, ZHANG Yuqiong. Expression and diagnostic value of high mobility group A2， carbohydrate antigen 125，and human epididymal protein 4 in ovarian epithelial carcinoma [J]. Oncology Progress, 2021, 19(18):1871-1873，1881.
[12] HEMPHILL J C Ⅲ , GREENBERG S M, ANDERSON C S,等 . 自发性脑出血诊疗指南 -美国心脏协会 /美国卒中协会的健康职业者指南 [J]. 文婉玲 , 于瀛 , 黄清海 ,等译 .中国脑血管病杂志 ,2015,12(9):490-504. HEMPHILL J C Ⅲ , GREENBERG S M, ANDERSON C S,et al. Guidelines for the diagnosis and treatment of spontaneous intracerebral hemorrhage: American Heart Association/American Stroke Association guidelines for health professionals[J]. WEN Wanling, YU Ying, HUANG Qinghai ,et al trans. Chinese Journal of Cerebrovascular Diseases, 2015, 12(9):490-504.
[13] SABER H, SAVER J L. Distributional validity and prognostic power of the National Institutes of Health Stroke Scale in US administrative claims data [J]. JAMA Neurol, 2020, 77(5):606-612.
[14] CHIU A H, HINCE D A, MCAULIffE W. Glasgow coma scale on presentation predicts outcome in endovascular treatment for acute posterior large-vessel occlusion [J]. AJNR Am J Neuroradiol, 2020, 41(4):645-649.
[15] ASKEW R L , CARMEN PT , SANGHA R , et al. Trade-offs in quality-of-life assessment between the modified Rankin Scale and Neuro-Qol measures -sciencedirect[J]. Value in Health, 2020, 23( 10):1366-1372.
[16] KEARNS K N, IRONSIDE N, PARK M S, et al. Neuroprotective therapies for spontaneous intracerebral hemorrhage[J]. Neurocritical Care,2021,35(3):862-886.
[17] 郑瑞娟 ,张耀龙 ,吴立爱 ,等 . 成人自发性脑出血患者临床预后不良危险因素分析 [J]. 临床军医杂志 ,2021,49(8):916-917,920. ZHENG Ruijuan, ZHANG Yaolong, WU Liai, et al. Analysis of risk factors for poor clinical prognosis in adult patients with spontaneous intracerebral hemorrhage[J]. Clinical Journal of Medical Officers, 2021, 49(8):916-917,920.
[18] YAMAMOTO S, KOH M, MATSUMURA K, et al. Impact of low ambient temperature on the occurrence of spontaneous intracerebral hemorrhage-analysis of population-based stroke registry in toyama, Japan [J]. J Stroke Cerebrovasc Dis, 2022, 31(1):106156.
[19] KUOHN L R, LEASURE A C, ACOSTA J N, et al. Cause of death in spontaneous intracerebral hemorrhage survivors multistate longitudinal study[J]. Neurology, 2020, 95(20): e2736-e2745.
[20] PASEBAN M, MARJANEH R M, BANACH M, et al. Modulation of microRNAs by aspirin in cardiovascular disease [J].Trends Cardiovasc Med, 2020, 30(5):249-254.
[21] PAN Guangtao, LIU Yuhan, SHANG Luorui, et al. EMT-associated microRNAs and their roles in cancer stemness and drug resistance[J]. Cancer Commun (Lond), 2021, 41(3):199-217.
[22] 王贺 , 赵长福 . miRNA-124在自发性脑出血患者血清中表达及其临床意义 [J]. 中国老年学杂志 , 2020, 40(22): 4729-4731. WANG He, ZHAO Changfu. Expression of miRNA-124 in serum of patients with spontaneous intracerebral hemorrhage and its clinical significance[J]. Chinese Journal of Gerontology, 2020, 40(22):4729-4731.
[23] BAI Ying, ZHANG Yuan, HAN Bing, et al. Circular RNA DLGAP4 Ameliorates ischemic stroke outcomes by targeting miR-143 to regulate endothelial-mesenchymal transition associated with blood-brain barrier integrity[J]. The Journal of Neuroscience,2018,38(1):32-50.
[24] YANG Xiaobo, GUO Zongduo, CAO Fang, et al. Rs41291957 polymorphism in the promoter region of microRNA 143 serves as a prognostic biomarker for patients with intracranial hemorrhage[J]. Mol Med Rep, 2021, 23(4):295.
[25] 郭春宣 ,钟纯正 ,李琦 ,等 . 循环 miR-143和 miR-182预测急性缺血性卒中患者转归的价值 [J]. 国际脑血管病杂志 ,2021,29(3):184-188. GUO Chunxuan, ZHONG Chunzheng, LI Qi, et al. Predictive value of circulating miR-143 and miR-182 for the outcome in patients with acute ischemic stroke [J]. International Journal of Cerebrovascular Diseases, 2021, 29(3):184-188.
[26] LI Yinuo, QIANG Wenan, GRIffiN B B, et al. HMGA2-mediated tumorigenesis through angiogenesis in leiomyoma [J]. Fertil Steril, 2020, 114(5):1085-1096.
[27] JIN Jun, ZHOU Feng, ZHU Jie, et al. MiR-26a inhibits the inflammatory response of microglia by targeting HMGA2 in intracerebral hemorrhage [J]. J Int Med Res, 2020, 48(6): 300060520929615.
[28] HUANG Shaoyue, HONG Zhen, ZHANG Leguo, et al. HMGA2 promotes brain injury in rats with cerebral infarction by activating TLR4/NF-κB signaling pathway[J]. Mediators Inflamm, 2022, 2022(1): 1376959.

备注/Memo

备注/Memo:
收稿日期：2022-09-02修回日期：2022-11-12
基金项目：北京市科学技术委员会科研计划项目（D191100000412004）。
作者简介：李长宝（1978-），男，硕士，副主任医师，研究方向：脑血管病、神经重症、脑外伤， E-mail：lichangbao674@163.com。
通讯作者：刘磊（1974-），男，博士，主任医师，研究方向：脑血管病、神经重症， E-mail：liulei301@126.com。

更新日期/Last Update: 2023-03-15