Correlation of serum CCL21 and NLRP3 with hemorrhagic conversion after mechanical thrombectomy in patients with cerebral infarction

doi:10.11958/20250110

Abstract

Abstract:

Objective To explore the correlation between serum chemokine C-C ligand 21 (CCL21), NOD like receptor protein 3 (NLRP3) and hemorrhagic transformation (HT) after mechanical thrombectomy in patients with acute cerebral infarction (ACI). Methods A total of 210 ACI patients who underwent mechanical thrombectomy were selected and divided into the HT group (19 cases) and the non HT group (191 cases) based on the re-examination of head CT 24-hours after treatment. The differences in clinical data and serum levels of CCL21 and NLRP3 were compared between two groups. Multivariate Logistic regression analysis was used to analyze the influencing factors of HT occurrence. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum CCL21 and NLRP3 for HT. Results The proportion of atrial fibrillation, anterior circulation infarction and preoperative National Institutes of Health Stroke Scale (NIHSS) scores were higher in the HT group than those in the non HT group (P<0.05). The preoperative serum levels of CCL21 and NLRP3 were higher in the HT group than those in the non HT group (P<0.05). The Logistic regression model analysis results showed that atrial fibrillation, anterior circulation infarction, preoperative NIHSS score, CCL21 and NLRP3 were risk factors for postoperative HT in ACI patients (P<0.05). The application of receiver operating characteristic (ROC) curve analysis results showed that the area under the curve (AUC) for predicting HT occurrence by CCL21 was 0.850 (95%CI: 0.763-0.936). The AUC predicted by NLRP3 was 0.787 (95%CI: 0.703-0.871), and the combined detection of the two further improved the predictive value (AUC=0.921, 95%CI: 0.867-0.976). Conclusion CCL21 and NLRP3 are closely related to the occurrence of HT in ACI patients after mechanical thrombectomy, and which are influencing factors for the occurrence of HT after mechanical thrombectomy.

Key words: acute cerebral infarction, hemorrhagic transformation, chemokine C-C motif ligand 21, NOD like receptor protein 3, mechanical thrombectomy

CLC Number:

R743.33

Figures/Tables 5

References 21

[1]	于振江, 王丽香, 贾文歆. 半乳糖凝集素3和内皮细胞特异性分子1与老年脑梗死患者术后出血转化的相关性研究[J]. 中华老年心脑血管病杂志, 2022, 24(6):626-629.
	YU Z J, WANG L X, JIA W X. Study on the correlation between galectin-3 and endothelial cell specific molecule 1 and postoperative bleeding transformation in elderly patients with cerebral infarction[J]. Chinese Journal of Geriatric Cardiovascular and Cerebrovascular Diseases, 2022, 24(6):626-629. doi:10.3969/j.issn.1009-0126.2022.06.018.
[2]	王丹, 王功锦, 赵学渊, 等. 血清基质金属蛋白酶9预测大血管闭塞性脑卒中患者机械取栓术后出血转化的临床研究[J]. 中华老年心脑血管病杂志, 2023, 25(7):720-724.
	WANG D, WANG G J, ZHAO X Y, et al. Clinical study on the prediction of bleeding transformation after mechanical thrombectomy in patients with large vessel occlusive stroke using serum matrix met alloproteinase-9[J]. Chinese Journal of Geriatric Cardiovascular and Cerebrovascular Diseases, 2023, 25(7):720-724. doi:10.3969/j.issn.1009-0126.2023.07.013.
[3]	王维, 李振东, 张诚诚, 等. 线粒体自噬参与NLRP3介导的炎症反应在脑卒中康复中的作用[J]. 中风与神经疾病杂志, 2022, 39(8):689-693.
	WANG W, LI Z D, ZHANG C C, et al. The role of mitochondrial autophagy in NLRP3 mediated inflammatory response in stroke rehabilitation[J]. Journal of Stroke and Neurological Disorders, 2022, 39(8):689-693. doi:10.19845/j.cnki.zfysjjbzz.2022.0174.
[4]	王强, 王萃, 赵燕, 等. 高血压脑出血术后脑水肿患者血清CC类趋化因子配体5和纤维蛋白原样蛋白2水平变化及意义[J]. 陕西医学杂志, 2023, 52(9):1181-1185.
	WANG Q, WANG C, ZHAO Y, et al. Changes and significance of serum CC chemokine ligand 5 and fibrinogen like protein 2 levels in patients with postoperative cerebral edema after hypertensive intracerebral hemorrhage[J]. Shaanxi Medical Journal, 2023, 52(9):1181-1185. doi:10.3969/j.issn.1000-7377.2023.09.015.
[5]	ANDE S R, GRYNSPAN J, AVIV R I, et al. Imaging for predicting hemorrhagic transformation of acute ischemic stroke-a narrative review[J]. Can Assoc Radiol J, 2022, 73(1):194-202. doi:10.1177/08465371211018369.
[6]	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, 中华医学会神经病学分会神经血管介入协作组. 中国急性缺血性脑卒中早期血管内介入诊疗指南2018[J]. 中华神经科杂志, 2018, 51(9):683-691.
	Chinese Medical Association Neurology Branch, Chinese Medical Association Neurology Branch Cerebrovascular Disease Group, Chinese Medical Association Neurology Branch Neurovascular Intervention Collaboration Group. Guidelines for early intravascular intervention diagnosis and treatment of acute ischemic stroke in China 2018[J]. Chinese Journal of Neurology, 2018, 51(9):683-691. doi:10.3760/cma.j.issn.1006-7876.2018.09.005.
[7]	韩冰莎, 李娇, 李翔, 等. 超声检测视神经鞘直径预测急性前循环缺血性脑卒中机械取栓术后出血转化的应用价值[J]. 中华神经医学杂志, 2020, 19(3):266-272.
	HAN B S, LI J, LI X, et al. The application value of ultrasound detection of optic nerve sheath diameter in predicting bleeding transformation after mechanical thrombectomy in acute anterior circulation ischemic stroke[J]. Chinese Journal of Neuromedicine, 2020, 19(3):266-272. doi:10.3760/cma.j.cn115354-20191231-00786.
[8]	GUO T, MA T, BAI X, et al. Intracranial hemorrhage risk in patients with cerebral microbleeds after mechanical thrombectomy for acute ischemic stroke:a systematic review and meta-analysis[J]. Neurol Sci, 2024, 45(7):3021-3029. doi:10.1007/s10072-024-07393-z.
[9]	张晓霞, 牛翠, 曹明善, 等. C-反应蛋白低密度脂蛋白胆固醇和嗜酸性粒细胞绝对值计数对急性脑梗死患者溶栓后出血转化的风险量化评估价值[J]. 中国急救医学, 2022, 42(5):416-420.
	ZHANG X X, NIU C, CAO M S, et al. The quantitative evaluation value of C-reactive protein low-density lipoprotein cholesterol and absolute eosinophil count for the risk of hemorrhagic transformation after thrombolysis in patients with acute cerebral infarction[J]. Chinese Journal of Emergency Medicine, 2022, 42(5):416-420. doi:10.3969/j.issn.1002-1949.2022.05.008.
[10]	QU X, XU Y, WANG L, et al. Analysis of relevant factors affecting the prognosis of mechanical thrombectomy in patients with acute posterior circulation large vessel occlusion cerebral infarction[J]. Neuroradiology, 2024, 66(12):2253-2260. doi:10.1007/s00234-024-03469-x.
[11]	AGBONON R, FORESTIER G, BRICOUT N, et al. Cerebral microbleeds and risk of symptomatic hemorrhagic transformation following mechanical thrombectomy for large vessel ischemic stroke[J]. J Neurol, 2024, 271(5):2631-2638. doi:10.1007/s00415-024-12205-7.
[12]	张蕊, 江俊莹, 戴琦, 等. 趋化因子CCL21及其受体CCR7在缺血性脑白质损伤中的表达及作用[J]. 国际脑血管病杂志, 2020, 28(7):530-535.
	ZHANG R, JIANG J Y, DAI Q, et al. Expression and role of chemokine CCL21 and its receptor CCR7 in ischemic white matter injury[J]. International Journal of Cerebrovascular Disease, 2020, 28(7):530-535. doi:10.3760/cma.j.issn.1673-4165.2020.07.009.
[13]	周桂银, 赵元丹, 高扬, 等. 趋化因子配体21对小鼠脑出血后继发性炎性损伤的作用研究[J]. 中国脑血管病杂志, 2020, 17(10):602-609.
	ZHOU G Y, ZHAO Y D, GAO Y, et al. Study on the effect of chemokine ligand 21 on secondary inflammatory injury after cerebral hemorrhage in mice[J]. Chinese Journal of Cerebrovascular Disease, 2020, 17(10):602-609.doi:10.3969/j.issn.1672-5921.2020.10.006.
[14]	LU H, GUO T, ZHANG Y, et al. Endoplasmic reticulum stress-induced NLRP3 inflammasome activation as a novel mechanism of polystyrene microplastics(PS-MPs)-induced pulmonary inflammation in chickens[J]. Zhejiang Univ Sci B, 2024, 25(3):233-243. doi:10.1631/jzus.B2300409.
[15]	XU J, HUANG S. Omentin-1 may be one treatment factor for intravenous thrombolysis of acute cerebral infarction through the inhibition of NLRP3 ubiquitination by ampk function:preliminary findings[J]. Neurology India, 2024, 72(2):309-318. doi:10.4103/ni.ni_1325_21.
[16]	田伟, 杨华, 高岩, 等. 急性前循环大血管闭塞性脑卒中合并房颤患者行直接机械取栓治疗取栓方式的临床效果[J]. 国际检验医学杂志, 2022, 43(20):2496-2500.
	TIAN W, YANG H, GAO Y, et al. Clinical effect of direct mechanical thrombectomy in patients with acute anterior circulation large vessel occlusion stroke complicated with atrial fibrillation[J]. International Journal of Laboratory Medicine, 2022, 43(20):2496-2500. doi:10.3969/j.issn.1673-4130.2022.20.012.
[17]	KIDOGUCHI M, AKAZAWA A, KOMORI O, et al. Prediction of occurrence of cerebral infarction after successful mechanical thrombectomy for ischemic stroke in the anterior circulation by arterial spin labeling[J]. Clin Neuroradiol, 2023, 33(4):965-971. doi:10.1007/s00062-023-01295-x.
[18]	崔大勇, 王新, 张博. 血清及脑脊液NLRP3、PCT、CRP水平对脑出血微创穿刺术后颅内感染的诊断价值[J]. 中国实验诊断学, 2020, 24(3):421-423.
	CUI D Y, WANG X, ZHANG B. The diagnostic value of serum and cerebrospinal fluid NLRP3,PCT,and CRP levels for intracranial infection after minimally invasive puncture surgery for cerebral hemorrhage[J]. Chinese Journal of Experimental Diagnosis, 2020, 24(3):421-423. doi:10.3969/j.issn.1007-4287.2020.03.013.
[19]	孙占玉, 郭智霖, 王上桥. 血清PTX3和NLRP3联合检测在颅脑损伤术后颅内感染早期诊治中的应用研究[J]. 热带医学杂志, 2022, 22(6):837-841.
	SUN Z Y, GUO Z L, WANG S Q. Application of combined detection of serum PTX3 and NLRP3 in early diagnosis and treatment of intracranial infection after traumatic brain injury[J]. Journal of Tropical Medicine, 2022, 22(6):837-841. doi:10.3969/j.issn.1672-3619.2022.06.020.
[20]	CHEN J, HUANG C, HONG C, et al. Regression analysis of bleeding factors and the correlation between FPE and NLR after mechanical thrombectomy for acute anterior circulation large vessel occlusion[J]. Biotechnol Genet Eng Rev, 2024, 40(1):692-703. doi:10.1080/02648725.2023.2186611.
[21]	SHANG K, ZHU W, YE L, et al. Effect of mechanical thrombectomy with and without intravenous thrombolysis on the functional outcome of patients with different degrees of thrombus perviousness[J]. Neuroradiology, 2023, 65(11):1657-1663. doi:10.1007/s00234-023-03210-0.

组别	n			性别（男/女）			年龄/岁			BMI/（kg/m²）			吸烟史
非HT组	191			100/91			66.97±6.93			24.89±3.70			98（51.3）
HT组	19			13/6			67.63±6.41			23.90±2.76			7（36.8）
χ²或t				1.794			0.400			1.133			1.447
组别			高血压		糖尿病			心房颤动			前循环梗死
非HT组			99（51.8）		96（50.3）			70（36.6）			30（15.7）
HT组			12（63.2）		8（42.1）			12（63.2）			8（42.1）
χ²			0.890		0.460			5.102^＊			6.442^＊
组别		术前NIHSS 评分/分				术前取栓			抗血小板聚集药物			抗凝药物
非HT组		11.26±1.01				4（2.1）			44（23.0）			50（26.2）
HT组		15.89±2.62				2（10.5）			7（36.8）			5（26.3）
t或χ²		15.559^＊＊				0.956			1.119			0.000

组别	n			性别（男/女）			年龄/岁			BMI/（kg/m²）			吸烟史
非HT组	191			100/91			66.97±6.93			24.89±3.70			98（51.3）
HT组	19			13/6			67.63±6.41			23.90±2.76			7（36.8）
χ²或t				1.794			0.400			1.133			1.447
组别			高血压		糖尿病			心房颤动			前循环梗死
非HT组			99（51.8）		96（50.3）			70（36.6）			30（15.7）
HT组			12（63.2）		8（42.1）			12（63.2）			8（42.1）
χ²			0.890		0.460			5.102^＊			6.442^＊
组别		术前NIHSS 评分/分				术前取栓			抗血小板聚集药物			抗凝药物
非HT组		11.26±1.01				4（2.1）			44（23.0）			50（26.2）
HT组		15.89±2.62				2（10.5）			7（36.8）			5（26.3）
t或χ²		15.559^＊＊				0.956			1.119			0.000

组别	n	CCL21	NLRP3
非HT组	191	671.33±24.91	99.25±9.21
HT组	19	704.97±22.28	108.52±7.68
t		5.661^＊＊	4.240^＊＊

组别	n	CCL21	NLRP3
非HT组	191	671.33±24.91	99.25±9.21
HT组	19	704.97±22.28	108.52±7.68
t		5.661^＊＊	4.240^＊＊

因素	β	SE	Wald χ²	P	OR（95%CI）
心房颤动	0.665	0.275	5.868	0.015	1.945（1.135~3.331）
前循环梗死	0.696	0.276	6.335	0.012	2.005（1.166~3.447）
术前NIHSS评分	0.987	0.281	12.457	<0.001	2.683（1.547~4.651）
CCL21	0.832	0.152	30.021	<0.001	2.298（1.707~3.095）
NLRP3	0.741	0.150	24.419	<0.001	2.098（1.564~2.815）
常数项	-1.881	0.303	38.638	<0.001	0.152