[1]郭继勃a,钟 曌b,郭 昊c,等.急性缺血性脑卒中患者血浆LIPCAR 和MMP-9 水平与病情严重程度及溶栓治疗后认知功能的关系研究[J].现代检验医学杂志,2023,38(05):40-46.[doi:10.3969/j.issn.1671-7414.2023.05.008]
 GUO Jiboa,ZHONG Zhaob,GUO Haoc,et al.Study on the Relationship between Peripheral Blood LIPCAR, MMP-9 and Severity of Acute Ischemic Stroke and Cognitive Function after RT-PA Intravenous Thrombolysis[J].Journal of Modern Laboratory Medicine,2023,38(05):40-46.[doi:10.3969/j.issn.1671-7414.2023.05.008]
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急性缺血性脑卒中患者血浆LIPCAR 和MMP-9 水平与病情严重程度及溶栓治疗后认知功能的关系研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年05期
页码:
40-46
栏目:
论著
出版日期:
2023-09-15

文章信息/Info

Title:
Study on the Relationship between Peripheral Blood LIPCAR, MMP-9 and Severity of Acute Ischemic Stroke and Cognitive Function after RT-PA Intravenous Thrombolysis
文章编号:
1671-7414(2023)05-040-07
作者:
郭继勃1a钟 曌1b郭 昊1c韩晓婷2祝 刚1c孙世辉1b任佳封1b
(1. 空军军医大学第二附属医院a. 急诊科;b. 神经内科;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):
GUO Jibo1aZHONG Zhao1bGUO Hao1cHAN Xiaoting2ZHU Gang1cSUN Shihui1bREN Jiafeng1b
(1a. Department of Emergency;1b. Department of Neurology;1c. 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:
急性缺血性脑卒中长链非编码RNA 预测心脏重构基质金属蛋白酶9重组组织型纤溶酶原激活剂静脉溶栓神经功能缺损认知功能
分类号:
R743.33;R392.11
DOI:
10.3969/j.issn.1671-7414.2023.05.008
文献标志码:
A
摘要:
目的 探讨急性缺血性脑卒中(acute ischemic stroke,AIS)患者血浆长链非编码RNA 预测心脏重构(longnoncoding RNAs predicting cardiac remodeling,LIPCAR)、基质金属蛋白酶9(matrix metalloprotein 9,MMP-9)水平与病情严重程度及溶栓治疗后认知功能的相关性。方法 收集2019 年8 月~ 2021 年12 月在空军军医大学第二附属医院神经内科诊疗的90 例AIS 患者为病例组,另收集来该院体检中心体检的58 例健康者为对照组。采用酶联免疫法分别检测两组受试者血浆LIPCAR 和MMP-9 水平,分析两者表达的相关性。根据美国国立卫生研究院卒中量表(NationalInstitutes of Health Stroke Scale, NIHSS)对AIS 患者进行神经功能缺损严重程度评分,分析LIPCAR 和MMP-9 水平与入院NIHSS 评分之间的相关性。所有AIS 患者经重组组织型纤溶酶原激活剂( recombinant tissue plasminogen activator,RT-PA) 静脉溶栓治疗7 天后,依照蒙特利尔认知评估量表(Montreal cognitive assessment,MoCA)评分,将其分为认知功能恢复良好组(MoCA ≥ 26 分)和认知功能恢复不良组(MoCA < 26 分);分析LIPCAR,MMP-9 水平与MoCA 评分的相关性。Logistic 回归模型分析影响AIS 患者认知功能恢复的独立危险因素。结果 与对照组比较,AIS组患者血浆LIPCAR(4.30±1.05 mg/L vs 1.73±0.58 mg/L)和MMP-9 水平(437.85±119.48 mg/L vs 235.66±86.22 mg/L)显著升高,差异具有统计学意义(t=17.028, 11.147,均P < 0.05)。Pearson 相关性分析显示,LIPCAR 与MMP-9 水平呈正相关,且分别与入院NIHSS 评分呈显著正相关,差异有统计学意义(r=0.657,0.602,0.715,均P < 0.05)。RT-PA 治疗7 天后,AIS 患者53 例(58.89%)认知功能恢复良好,37 例(41.11%)认知功能恢复不良。与认知功能恢复不良组比较,认知功能恢复良好组LIPCAR 水平(3.76±0.32 mg/L vs 5.12±0.77 mg/L)和MMP-9 水平(385.46±102.45mg/L vs 512.63±114.36 mg/L)显著降低,差异有统计学意义(t=11.290,5.956,均P < 0.05)。认知功能恢复不良组患者LIPCAR,MMP-9 水平与MoCA 评分呈明显负相关,差异有统计学意义(r=-0.596,-0.674,均P < 0.05)。Logistic 回归分析显示,糖尿病、高血脂、高血压、空腹血糖(fasting blood glucose,FBG)、同型半胱氨酸(homocysteine,Hcy)、LIPCAR 和MMP-9 水平及入院NIHSS 评分是影响AIS 患者神经认知功能恢复的独立危险因素。结论 LIPCAR 和MMP-9 水平在AIS 患者外周血中显著增加,且与患者神经缺损程度呈正相关;经RT-PA 静脉溶栓治疗后,LIPCAR 和MMP-9 水平与患者认知功能恢复呈负相关,且是影响患者认知功能恢复的危险因素之一,可作为临床评估AIS 预后的不良危险因素。
Abstract:
Objective To investigate the relationship between the levels of plasma long chain noncoding RNA predicting cardiac remodeling(LIPCAR) and matrix metalloprotein-9 (MMP-9) in patients with acute ischemtic stroke(AIS) and the severity of disease and cognitive function after thrombolytic therapy. Methods 90 patients with AIS who were diagnosed and treated in the neurology department of the Second Affiliated Hospital of Air Force Military Medical University from August 2019 to December 2021 were collected as the case group, and 58 healthy individuals who came to the physical examination center of the hospital for physical examination were collected as the control group. The levels of LIPCAR and MMP-9 in peripheral blood of the two groups were detected by enzyme-linked immunoassay, and the correlation between the two expressions was analyzed. According to the National Institutes of Health Stroke Scale (NIHSS), AIS patients were scored for the severity of neurological impairment, and the correlation between LIPCAR, MMP-9 levels and admission NIHSS score was analyzed. After 7 days of intravenous thrombolytic therapy with recombinant tissue plasminogen activator (RT-PA), According to Montreal cognitive assessment (MoCA) score, they were divided into good cognitive recovery group (MoCA ≥ 26 points) and poor cognitive recovery group (MoCA < 26 points). The correlation between LIPCAR, MMP-9 level and MoCA score was analyzed. Logistic regression model was used to analyze the independent risk factors affecting the recovery of neurocognitive function in patients with AIS. Results Compared with the control group, the levels of LIPCAR (4.30±1.05mg/L vs 1.73±0.58mg/L) and MMP-9 (437.85 ± 119.48mg/L vs 235.66 ± 86.22mg/L) in peripheral blood of patients in AIS group were significantly higher, with statistically significant differences (t=17.028, 11.147, all P<0.05). Pearson correlation analysis showed that LIPCAR and MMP-9 levels were correlated with each other, and were positively correlated with NIHSS scores on admission, with statistical significance (r=0.657,0.602,0.715,all P<0.05). After 7 days of treatment with RT-PA, 53 patients (58.89%) had good cognitive function recovery and 37 patients (41.11%) had poor cognitive function recovery. Compared with the group with poor cognitive function recovery, the level of LIPCAR (3.76±0.32 mg/L vs 5.12±0.77 mg/L) and MMP-9 (385.46±102.45 mg/L vs 512.63±114.36 mg/L) in the group with good cognitive function recovery were significantly lower, and the difference was statistically significant (t=11.290,5.956, all P<0.05). The levels of LIPCAR and MMP-9 in the poor cognitive function recovery group were significantly negatively correlated with the MoCA score, and the difference was statistically significant (r=-0.596, -0.674, all P<0.05). Logistic regression analysis showed that diabetes, hyperlipidemia, hypertension, fasting blood glucose (FBG), homocysteine (Hcy), LIPCAR, MMP-9 levels and NIHSS score on admission were independent risk factors affecting the recovery of neurocognitive function in AIS patients. Conclusion The levels of LIPCAR and MMP-9 in the peripheral blood of AIS patients were significantly increased, and were positively correlated with the degree of neurological deficit in patients. After intravenous thrombolytic therapy with RT-PA, LIPCAR and MMP-9 levels are negatively correlated with the recovery of cognitive function in patients, and are one of the risk factors affecting the recovery of cognitive function in patients, which can be used as adverse risk factors for clinical assessment of AIS prognosis.

参考文献/References:

[1] MEYERS P M, SCHUMACHER H C, CONNOLLY E S, et al. Current status of endovascular stroke treatment[J]. Circulation, 2011, 123(22): 2591-2601.
[2] WACH-KLINK A, PACIURA K, ZWADOWSKA A, et al. The impact of selected cardiovascular factors on the safety and efficacy of intravenous thrombolysis for acute ischemic stroke in routine practice in a rural hospital[J]. Medical Studies, 2018, 34(3): 232-240.
[3] SANTER L, L?PEZ B, RAVASSA S, et al. Circulating long noncoding RNA LIPCAR predicts heart failure outcomes in patients without chronic kidney disease[J].Hypertension, 2019, 73(4): 820-828.
[4] MEESSEN J M T A, B?R C B, DI DONA F M, et al. LIPCAR is increased in chronic symptomatic HF patients. A sub-study of the GISSI-HF trial[J]. Clinical Chemistry, 2021, 67(12): 1721-1731.
[5] LI Meng, WANG Yuefeng, YANG Xinchun, et al. Circulating long noncoding RNA LIPCAR acts as a novel biomarker in patients with ST-segment elevation myocardial infarction[J]. Medical Science Monitor, 2018, 24(14): 5064-5070.
[6] 余天浩, 李瑜辉, 伍灏堃, 等. 血清LncRNA LIPCAR 在冠心病并抑郁的表达及与临床特征的关系[J].广东医学, 2018, 39(21): 3182- 3186. YU Tianhao, LI Yuhui, WU Haokun, et al. Expression of serum LncRNA LIPCAR in patients with coronary heart disease and depression and its correlation with clinical features [J]. Guangdong Medical Journal, 2018, 39(21): 3182- 3186.
[7] 马宾, 李华欣, 袁梅.MMP-9 基因rs3918242 多态性与缺血性脑卒中的研究进展[J]. 医学综述, 2022,28(8): 1485-1490. MA Bin, LI Huaxin, YUAN Mei. Research progress of MMP-9 gene rs3918242 polymorphism and ischemic stroke[J]. Medical Recapitulate, 2022, 28(8): 1485-1490.
[8] ZHANG Wen, SONG Junke, ZHANG Xue, et al. Salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by protecting the blood brain barrier through MMP-9 inhibition and antiinflammation[J]. Chinese Journal of Natural Medicines, 2018, 16(3): 184-193.
[9] 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. Society of Neurology of Chinese Medical Association, Group of Cerebrovascular Diseases Society of Neurology, Chinese Medical Association. Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018 [J].Chinese Journal of Neurology, 2018, 51(9): 666-682.
[10] FITZGERALD S, MEREUTA O M, DOYLE K M, et al. Correlation of imaging and histopathology of thrombi in acute ischemic stroke with etiology and outcome[J]. Journal of Neurosurgical Sciences, 2019, 63(3): 292-300.
[11] HAN Yingying, LI Gang, TANG Yueyu, et al. Effect of rt-PA intravenous thrombolysis on the prognosis of patients with minor ischemic stroke[J]. Neurological Research, 2021, 43(8): 653-658.
[12] ZHU Wenli, TIAN Lili, YUE Xuanye, et al. LncRNA expression profiling of ischemic stroke during the transition from the acute to subacute stage [J]. Frontiers in Neurology, 2019, 10: 36.
[13] CHEN Shengcai, WANG Mengdie, YANG Hang, et al. LncRNA TUG1 sponges microRNA-9 to promote neurons apoptosis by up-regulated Bcl2l11 under ischemia[J]. Biochemical and Biophysical Research Communications, 2017, 485(1): 167-173.
[14] WANG Shengwen, LIU Zhong, SHI Zhongsong. Non-coding RNA in acute ischemic stroke: mechanisms, biomarkers and therapeutic targets[J]. Cell Transplantation, 2018, 27(12): 1763-1777.
[15] LIU Cuiying, YANG Jian, ZHANG Chengcheng, et al. Analysis of long non-coding RNA expression profiles following focal cerebral ischemia in mice[J].Neuroscience Letters, 2018, 665: 123-129.
[16] KUMARSWAMY R, BAUTERS C, VOLKMANN I, et al. Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure[J]. Circulation Research, 2014, 114(10): 1569-1575.
[17] 王蕾, 王学惠, 潘亚婷, 等.LIPCAR 在慢性心力衰竭及合并肾功能不全患者循环中的表达[J]. 中国动脉硬化杂志, 2018, 26(4): 384-388. WANG Lei, WANG Xuehui, PAN Yating, et al. Expression of circulating LIPCAR in patients with chronic heart failure and combined renal insufficiency[J]. Chinese Journal of Arteriosclerosis, 2018, 26(4): 384-388.
[18] SHI Yue, FAN Xuehui, LI Guozhong, et al. Association of serum dystroglycan,MMP-2/9 and AQP-4 with haematoma expansion in patients with intracerebral haemorrhage[J]. Neuropsychiatric Disease and Treatment, 2021, 17: 11-18.
[19] ZHANG Haifang, ZHAO Wenjing. Resveratrol alleviates ischemic brain injury by inhibiting the activation of Pro-Inflammatory microglia via the CD147/MMP-9 pathway[J]. Journal of Stroke and Cerebrovascular Diseases, 2022, 31(4): 106307.
[20] 谢馨, 周新平, 范进.血清Galectin-3、MMP-9 表达与急性缺血性脑卒中患者静脉溶栓治疗后神经功能缺损的相关性[J]. 中风与神经疾病杂志, 2022,39(8): 719-722. XIE Xin, ZHOU Xinping, FAN Jin. Correlation between serum galectin-3,MMP-9 expression and neurological deficit after intravenous thrombolysis in patients with acute ischemic stroke[J]. Journal of Apoplexy and Nervous Diseases, 2022, 39(8): 719-722.
[21] 常青, 杨宇英, 薛茜, 等.NLR, MMP-9 对急性缺血性脑卒中静脉溶栓患者出血转化的诊断价值[J]. 中国老年学杂志, 2022, 42(9): 2077-2081. CHANG Qing, YANG Yuying, XUE Qian, et al. Diagnostic value of NLR and MMP-9 for hemorrhagic transformation in patients with acute ischemic stroke with intravenous thrombolysis[J]. Chinese Journal of Gerontology, 2022, 42(9): 2077-2081.

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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 调控内质网应激调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:郭继勃(1989-),男,主治医师,急诊科,研究方向:脑卒中,癫痫,帕金森,E-mail:u2bsrr@163.com。
通讯作者:钟曌,女,主治医师,E-mail:53612410@qq.com。
更新日期/Last Update: 2023-09-15