TLR4 mRNA和HO-1水平在ICVD病情及预后评估中的价值

doi:10.3969/j.issn.1673-8640.2021.012.007

摘要/Abstract

摘要：

目的探讨Toll样受体（TLR）4 mRNA和血红素氧合酶-1（HO-1）在缺血性脑血管病（ICVD）病情及预后评估中的价值。方法选取ICVD患者324例（ICVD组）、体检健康者324名（正常对照组）。分别检测HO-1水平及外周血TLR4 mRNA相对表达量。根据美国国立卫生研究院卒中量表（NIHSS）评分将ICVD患者分为轻度损伤组、中度损伤组和重度损伤组。根据头颅多普勒超声检查结果将ICVD患者分为轻度狭窄组、中度狭窄组和重度狭窄组。对ICVD患者随访6个月,根据随访结果分为预后较好组和预后不良组。采用Pearson相关分析评估HO-1及TLR4 mRNA与NIHSS评分的相关性,采用Spearman相关分析评估HO-1及TLR4 mRNA与颅内动脉狭窄程度的相关性。采用受试者工作特征（ROC）曲线评估HO-1及TLR4 mRNA判断ICVD预后的价值。结果 ICVD组HO-1水平及TLR4 mRNA相对表达量均高于正常对照组（P=0.000）。轻度狭窄组、中度狭窄组、重度狭窄组之间以及轻度损伤组、中度损伤组、重度损伤组之间HO-1水平及TLR4 mRNA相对表达量均依次升高,各组间差异均有统计学意义（P<0.05）。预后较好组HO-1水平及TLR4 mRNA相对表达量均低于预后不良组（P<0.05）。ICVD组HO-1水平及TLR4 mRNA相对表达量与颅动脉狭窄程度、NIHSS评分均呈正相关（P<0.05）。ROC曲线分析结果显示,HO-1、TLR4 mRNA判断ICVD预后不良的最佳临界值分别为4.364 ng/mL、0.989,曲线下面积分别为0.800、0.815,敏感性分别为81.4%、85.1%,特异性分别为72.4%、73.5%。结论 HO-1及TLR4或可作为ICVD患者病情评估及预后判断的有效指标。

关键词: 血红素氧合酶-1, Toll样受体4 mRNA, 缺血性脑血管病, 病情评估, 预后

Abstract:

Objective To investigate the roles of heme oxygenase-1（HO-1） and Toll-like receptor（TLR） 4 mRNA in evaluating the condition and prognosis of ischemic cerebrovascular disease（ICVD）. Methods Totally,324 patients with ICVD（ICVD group） and 324 healthy subjects（control group） were enrolled. HO-1 level and TLR4 mRNA expression in peripheral blood were determined. According to the National Institutes of Health Stroke Scale（NIHSS）score,ICVD patients were classified into mild injury group,moderate injury group and severe injury group. According to the results of head Doppler ultrasound,ICVD patients were classified into mild stenosis group,moderate stenosis group and severe stenosis group. These patients with ICVD were followed up for 6 months. According to the follow-up results,they were classified into good prognosis group and poor prognosis group. Pearson correlation analysis was used to evaluate the correlation between HO-1,TLR4 mRNA and NIHSS score. Spearman correlation analysis was used to evaluate the correlation between HO-1,TLR4 mRNA and the degree of intracranial artery stenosis. Receiver operating characteristic（ROC） curve was used to evaluate the prognostic value of HO-1 and TLR4 mRNA in ICVD. Results HO-1 level and TLR4 mRNA expression in ICVD group were higher than those in control group（P=0.000）. HO-1 level and TLR4 mRNA expression in mild stenosis group,moderate stenosis group,severe stenosis group and mild injury group,moderate injury group and severe injury group were increased in turn（P<0.05）. The HO-1 level and TLR4 mRNA expression in good prognosis group were lower than those in poor prognosis group（P<0.05）. In ICVD group,HO-1 level and TLR4 mRNA expression were positively correlated with stenosis degree and NIHSS score（P<0.05）. ROC curve analysis showed that the optimal cut-off values of HO-1 and TLR4 mRNA for predicting ICVD prognosis were 4.364 ng/mL and 0.989,the areas under curves were 0.800 and 0.815,the sensitivities were 81.4% and 85.1%,and the specificities were 72.4% and 73.5%,respectively. Conclusions HO-1 and TLR4 may be used as effective indicators for evaluating the condition and prognosis of ICVD patients.

Key words: Heme oxygenase-1, Toll-like receptor 4 mRNA, Ischemic cerebrovascular disease, Condition assessment, Prognosis

中图分类号:

Q556

樊明鹤, 林广民, 黄瑞杰. TLR4 mRNA和HO-1水平在ICVD病情及预后评估中的价值[J]. 检验医学, 2021, 36(12): 1229-1233.

FAN Minghe, LIN Guangmin, HUANG Ruijie. TLR4 mRNA and HO-1 level in evaluating the condition and prognosis of ICVD[J]. Laboratory Medicine, 2021, 36(12): 1229-1233.

图/表 8

参考文献 18

[1]	BONDONNO C P, BLEKKENHORST L C, PRINCE R L, et al. Association of vegetable nitrate intake with carotid atherosclerosis and ischemic cerebrovascular disease in older women[J]. Stroke, 2017, 48(7):1724-1729. DOI URL
[2]	王胜奎, 周俊. 小而密低密度脂蛋白胆固醇在心脑血管系统相关疾病中的意义[J]. 检验医学, 2019, 34(1):19-22.
[3]	DEL BRUTTO V J, CHATURVEDI S, DIENER H C, et al. Antithrombotic therapy to prevent recurrent strokes in ischemic cerebrovascular disease:JACC Scientific Expert Panel[J]. J Am Coll Cardiol, 2019, 74(6):786-803. DOI URL
[4]	ALGIN A, ERDOGAN M O, AYDIN I, et al. Clinical usefulness of brain-derived neurotrophic factor and visinin-like protein-1 in early diagnostic tests for acute stroke[J]. Am J Emerg Med, 2019, 37(11):2051-2054. DOI URL
[5]	ALI T, KIM T, REHMAN S U, et al. Natural dietary supplementation of anthocyanins via PI3K/Akt/Nrf2/HO-1 pathways mitigate oxidative stress,neurodegeneration,and memory impairment in a mouse model of Alzheimer's disease[J]. Mol Neurobiol, 2017, 55(7):6076-6093. DOI URL
[6]	XIONG J, WANG K, YUAN C, et al. Luteolin protects mice from severe acute pancreatitis by exerting HO-1-mediated anti-inflammatory and antioxidant effects[J]. Int J Mol Med, 2017, 39(1):113-125. DOI URL
[7]	TARTEY S, TAKEUCHI O . Pathogen recognition and Toll-like receptor targeted therapeutics in innate immune cells[J]. Int Rev Immunol, 2017, 36(2):57-73. DOI URL
[8]	各类脑血管疾病诊断要点[J]. 中华神经科杂志, 1996, 42(6):60-61.
[9]	OLIVATO S, NIZZOLI S, CAVAZZUTI M, et al. e-NIHSS:an expanded national institutes of health stroke scale weighted for anterior and posterior circulation strokes[J]. J Stroke Cerebrovasc Dis, 2016, 25(12):2953-2957. DOI URL
[10]	脑卒中患者临床神经功能缺损程度评分标准(1995)[J]. 中华神经科杂志, 1996, 42(6):62-64.
[11]	赵薇, 王树, 李方江. 大黄酚对小鼠脑缺血/再灌注脑组织抗氧化应激和AQP4的影响[J]. 中国药理学通报, 2015, 31(10):1477-1478.
[12]	李谌, 黄维义. 血红素氧合酶1的生物学特性及其在冠心病防治中的作用[J]. 中国动脉硬化杂志, 2016, 24(1):92-96.
[13]	CHAN K H, NG M K, STOCKER R. Haem oxygenase-1 and cardiovascular disease:mechanisms and therapeutic potential[J]. Clin Sci(Lond), 2011, 120(12):493-504. DOI URL
[14]	DURANTE W. Protective role of heme oxygenase-1 against inflammation in atherosclerosis[J]. Front Biosci(Landmark Ed), 2011, 16:2371-2388.
[15]	DOLASIA K, BISHT M K, PRADHAN G, et al. TLRs/NLRs:shaping the landscape of host immunity[J]. Int Rev Immunol, 2018, 37(1):3-19. DOI URL
[16]	RAHIMIFARD M, MAQBOOL F, MOEINI-NODEH S, et al. Targeting the TLR4 signaling pathway by polyphenols:a novel therapeutic strategy for neuroinflammation[J]. Ageing Res Rev, 2017, 36:11-19. DOI URL
[17]	王艳, 兰坚, 何顺学. 血清血管内皮生长因子、Toll样受体与颈动脉支架成形术治疗急性缺血性脑卒中患者预后的相关性研究[J]. 实用医院临床杂志, 2019, 16(1):30-32.
[18]	方玲, 刘先哲. 血管内皮细胞TLR2与动脉粥样硬化发展关系的研究进展[J]. 医学综述, 2008, 14(4):499-500.

引物名称	序列（5'~3'）	引物大小/bp
TLR4	上游 TGGATACGTTTCTTATAA	111
	下游 GAAATGGAGGCACCCCTT
β-actin	上游 GAGCCTCGCCTTTGCCGATCC	139
	下游 CGATGCCGTCTCGATGGGG

引物名称	序列（5'~3'）	引物大小/bp
TLR4	上游 TGGATACGTTTCTTATAA	111
	下游 GAAATGGAGGCACCCCTT
β-actin	上游 GAGCCTCGCCTTTGCCGATCC	139
	下游 CGATGCCGTCTCGATGGGG

组别	例数	吸烟史		饮酒史		高血压史		糖尿病史		心脏疾病史		高脂血症
组别	例数	有	无	有	无	有	无	有	无	有	无	有	无
ICVD组	324	163	161	138	185	82	242	79	245	95	229	73	251
正常对照组	324	68	256	70	254	34	290	31	293	38	286	24	300
χ²值		63.605		34.446		26.602		27.907		33.336		32.718
P值		<0.001		<0.001		<0.001		<0.001		<0.001		<0.001

组别	例数	吸烟史		饮酒史		高血压史		糖尿病史		心脏疾病史		高脂血症
组别	例数	有	无	有	无	有	无	有	无	有	无	有	无
ICVD组	324	163	161	138	185	82	242	79	245	95	229	73	251
正常对照组	324	68	256	70	254	34	290	31	293	38	286	24	300
χ²值		63.605		34.446		26.602		27.907		33.336		32.718
P值		<0.001		<0.001		<0.001		<0.001		<0.001		<0.001

组别	例数	HO-1/（ng/mL）	TLR4 mRNA
ICVD组	324	4.18±2.52	1.21±0.57
正常对照组	324	2.10±1.11	0.31±0.10
t值		10.369	27.994
P值		0.000	0.000