Roles of Ang-1，HO-1，NGF and MMSE scores in evaluation of HICH efficacy

doi:10.3969/j.issn.1673-8640.2024.07.006

Abstract

Abstract:

Objective To evaluate the efficacy of angiopoietin-1（Ang-1），heme oxygenase 1（HO-1），nerve growth factor （NGF） and Mini-Mental State Examination（MMSE）score in hypertensive intracerebral hemorrhage （HICH）. Methods Totally，152 patients with HICH（HICH group）and 68 healthy subjects （healthy control group） were enrolled from Zhangjiakou First Hospital from February 2018 to February 2022. All the patients were treated with bone flap hematoma removal，supportive therapy and brain proteolytic hydrolysate. According to the efficacy，they were classified into effective group （105 cases） and ineffective group （47 cases）. Serum Ang-1，HO-1 and NGF levels of HICH and healthy groups before and after treatment were determined，and MMSE scores were used to evaluate the cognitive function of HICH patients. Multivariate Logistic regression analysis was used to evaluate the risk factors of HICH treatment failure. Receiver operating characteristic （ROC） curve was used to evaluate the efficacy of Ang-1，HO-1，NGF and MMSE scores in judging the therapeutic effect of HICH. Results Before treatment，serum Ang-1，NGF and MMSE scores in HICH group were lower than those in healthy control group （P<0.05），and serum HO-1 levels in HICH group were higher than those in healthy control group （P<0.05）. After treatment，serum Ang-1，NGF and MMSE scores in effective group were higher than those before treatment （P<0.05），and serum HO-1 levels were lower（P<0.05）. There was no statistical significance between the 2 groups before and after treatment （P>0.05）. Serum Ang-1，NGF levels and MMSE scores in ineffective group were lower than those in effective group before and after treatment （P<0.05），and serum HO-1 levels were higher than those in effective group （P<0.05）. Grade 3 hypertension and pre-treatment increase of HO-1，decrease of Ang-1，decrease of NGF and decrease of MMSE scores were risk factors for treatment ineffectiveness in patients with HICH [odds ratios （OR） were 2.324，1.442，0.549，0.671 and 0.716，95% confidence intervals （CI） were 1.357-5.468，1.203-4.535，0.211-0.884，0.316-0.854 and 0.461-0.973，respectively，P<0.05]. The areas under curves （AUC） of serum Ang-1，HO-1，NGF levels and MMSE scores and combined determination to judge the treatment efficacy of HICH were 0.859，0.848，0.856，0.820 and 0.958. Conclusions Serum Ang-1，NGF and HO-1 levels are related to the clinical efficacy of patients with HICH，and they may be used as potential indicators for the efficacy evaluation of HICH.

Key words: Angiopoietin-1, Heme oxidase 1, Nerve growth factor, Hypertensive intracerebral hemorrhage, Cognitive impairment

CLC Number:

R446.1

ZHANG Chunxiang, JI Mingming, SUN Minling, LI Jianying. Roles of Ang-1，HO-1，NGF and MMSE scores in evaluation of HICH efficacy[J]. Laboratory Medicine, 2024, 39(7): 650-655.

Figures/Tables 6

References 23

[1]	胡兵, 李改, 张会敏. 血清IL-6、DD水平在预测高血压患者脑出血风险中的作用[J]. 检验医学, 2022, 37(1):63-67. DOI
[2]	刘瑞, 万里. 注射用脑蛋白水解物对高血压脑出血患者脑水肿与神经功能的影响[J]. 山西医药杂志, 2020, 49(24):3427-3429.
[3]	MOXON J V, TROLLOPE A F, DEWDNEY B, et al. The effect of angiopoietin-1 upregulation on the outcome of acute ischaemic stroke in rodent models:a meta-analysis[J]. J Cereb Blood Flow Metab, 2019, 39(12):2343-2354.
[4]	BERECZKI D Jr, BALLA J. Heme oxygenase-1:clinical relevance in ischemic stroke[J]. Curr Pharm Des, 2018, 24(20):2229-2235.
[5]	LUAN X, QIU H, HONG X, et al. High serum nerve growth factor concentrations are associated with good functional outcome at 3 months following acute ischemic stroke[J]. Clin Chim Acta, 2019, 488:20-24.
[6]	吴金波, 杨春兰, 姚振兴, 等. 血清sRAGE、25-羟维生素-D3、NLRP3 mRNA与高血压脑出血患者发生认知功能损害的关系[J]. 中国医师杂志, 2021, 23(10):1492-1495.
[7]	GALEA M, WOODWARD M. Mini-mental state examination(MMSE)[J]. Aust J Physiother, 2005, 51(3):198.
[8]	中国高血压防治指南修订委员会. 中国高血压防治指南2010[J]. 中华高血压杂志, 2011, 19(8):701-743.
[9]	中华医学会神经外科学分会, 中国医师协会急诊医师分会, 国家卫生和计划生育委员会脑卒中筛查与防治工程委员会. 自发性脑出血诊断治疗中国多学科专家共识[J]. 中华急诊医学杂志, 2015, 24(12):1319-1323.
[10]	1995年我国第四次脑血管病学术会议. 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, 29(6): 381-383.
[11]	JONES C. Glasgow coma scale[J]. Am J Nurs, 1979, 79(9):1551-1553. PMID
[12]	ASKIM T, BEMHRADT J, CHURILOV L, et al. The Scandinavian Stroke Scale is equaly as good as the National Institutes of Health Stroke Scale in identifying 3-month outcome[J]. J Rehabil Med, 2016, 48(10):909-912.
[13]	黄金楷, 蔡刚峰, 黄国河, 等. 原发性高血压患者发生高血压性脑出血危险因素研究[J]. 华南预防医学, 2021, 47(10):1322-1324.
[14]	陈秀英, 左旭政, 程畅, 等. 血清SDF-1、Ang-1与急性缺血性脑卒中预后的关系及其预测价值[J]. 卒中与神经疾病, 2020, 27(2):166-170.
[15]	WALTER E R H, GE Y, MASON J C, et al. A coumarin-porphyrin FRET break-apart probe for heme oxygenase-1[J]. J Am Chem Soc, 2021, 143(17):6460-6469. DOI PMID
[16]	SUN Y, XU B, ZHANG Q. Nerve growth factor in combination with oxiracetam in the treatment of hypertensive cerebral hemorrhage[J]. Pak J Med Sci, 2018, 34(1):73-77. DOI PMID
[17]	VENKAT P, NING R, ZACHAREK A, et al. Treatment with an angiopoietin-1 mimetic peptide promotes neurological recovery after stroke in diabetic rats[J]. CNS Neurosci Ther, 2021, 27(1):48-59. DOI PMID
[18]	王昆, 罗小娜, 李时光, 等. Nrf2/HO-1信号通路在6-羟基多巴胺帕金森病模型大鼠神经损伤中的作用[J]. 中国医药生物技术, 2019, 14(3):237-244.
[19]	LEE T K, LEE J C, KIM D W, et al. Ischemia-reperfusion under hyperthermia increases heme oxygenase-1 in pyramidal neurons and astrocytes with accelerating neuronal loss in gerbil hippocampus[J]. Int J Mol Sci, 2021, 22(8):3963.
[20]	STEPANYAN A, ZZKHARYAN R, SIMONYAN A, et al. Involvement of polymorphisms of the nerve growth factor and its receptor encoding genes in the etiopathogenesis of ischemic stroke[J]. BMC Med Genet, 2018, 19(1):33. DOI PMID
[21]	LI X, LI F, LING L, et al. Intranasal administration of nerve growth factor promotes angiogenesis via activation of PI3K/Akt signaling following cerebral infarction in rats[J]. Am J Transl Res, 2018, 10(11):3481-3492. PMID
[22]	KAZIM S F, OGULNICK J V, ROBINSON M B, et al. Cognitive impairment after intracerebral hemorrhage:a systematic review and meta-analysis[J]. World Neurosurg, 2021, 148:141-162.
[23]	刘倩, 付本升, 钟毓贤, 等. 奥拉西坦联合脑蛋白水解物治疗脑卒中后认知功能障碍的临床疗效及对血清Hcy、hs-CRP水平的影响[J]. 广西医科大学学报, 2017, 34(12):1748-1751.

组别	例数	Ang-1/（ng·mL^-1）	HO-1/（ng·mL^-1）	NGF/（μg·mL^-1）	MMSE评分/分
HICH组	152	36.06±6.25	0.39±0.14	34.11±6.98	25.01±2.29
正常对照组	68	72.77±16.34	0.15±0.04	67.35±13.03	28.12±1.06
t值		-24.088	13.870	-24.579	-10.688
P值		<0.001	<0.001	<0.001	<0.001

组别	例数	Ang-1/（ng·mL^-1）	HO-1/（ng·mL^-1）	NGF/（μg·mL^-1）	MMSE评分/分
HICH组	152	36.06±6.25	0.39±0.14	34.11±6.98	25.01±2.29
正常对照组	68	72.77±16.34	0.15±0.04	67.35±13.03	28.12±1.06
t值		-24.088	13.870	-24.579	-10.688
P值		<0.001	<0.001	<0.001	<0.001

组别	例数	Ang-1/（ng·mL^-1）				HO-1/（ng·mL^-1）
组别	例数	治疗前	治疗后	t值	P值	治疗前	治疗后	t值	P值
无效组	47	29.36±4.67	31.11±6.45	-1.507	0.135	0.52±0.11	0.50±0.10	1.317	0.189
有效组	105	39.06±4.19	58.01±13.57	-13.673	<0.001	0.34±0.11	0.30±0.12	2.624	0.009
t值		-12.727	-12.934			9.324	9.976
P值		<0.001	<0.001			<0.001	<0.001
组别	NGF/（μg·mL^-1）					MMSE评分/分
组别	治疗前	治疗后	t值	P值		治疗前	治疗后	t值	P值
无效组	27.21±6.34	29.06±3.09	-1.798	0.075		22.33±1.56	23.14±2.35	-1.969	0.052
有效组	37.20±4.66	50.41±8.07	-14.526	<0.001		26.21±1.36	27.50±2.08	-5.319	<0.001
t值	-10.878	-17.544				-15.522	-11.468
P值	<0.001	<0.001				<0.001	<0.001

组别	例数	Ang-1/（ng·mL^-1）				HO-1/（ng·mL^-1）
组别	例数	治疗前	治疗后	t值	P值	治疗前	治疗后	t值	P值
无效组	47	29.36±4.67	31.11±6.45	-1.507	0.135	0.52±0.11	0.50±0.10	1.317	0.189
有效组	105	39.06±4.19	58.01±13.57	-13.673	<0.001	0.34±0.11	0.30±0.12	2.624	0.009
t值		-12.727	-12.934			9.324	9.976
P值		<0.001	<0.001			<0.001	<0.001
组别	NGF/（μg·mL^-1）					MMSE评分/分
组别	治疗前	治疗后	t值	P值		治疗前	治疗后	t值	P值
无效组	27.21±6.34	29.06±3.09	-1.798	0.075		22.33±1.56	23.14±2.35	-1.969	0.052
有效组	37.20±4.66	50.41±8.07	-14.526	<0.001		26.21±1.36	27.50±2.08	-5.319	<0.001
t值	-10.878	-17.544				-15.522	-11.468
P值	<0.001	<0.001				<0.001	<0.001

组别	例数	年龄/岁	性别		BMI/ （kg·m^-2）	吸烟史/ [例（%）]	饮酒史/ [例（%）]	家族（高血压）遗传史/[例（%）]
组别	例数	年龄/岁	男/[例（%）]	女/[例（%）]	BMI/ （kg·m^-2）	吸烟史/ [例（%）]	饮酒史/ [例（%）]	家族（高血压）遗传史/[例（%）]
无效组	47	65.02±9.12	29（61.70）	69（65.71）	23.41±1.06	28（59.57）	22（46.81）	15（31.91）
有效组	105	62.03 ±7.05	18（38.30）	36（34.29）	23.04±1.12	56（53.33）	51（48.57）	32（30.48）
统计值		2.2	0.228		1.913	0.512	0.04	0.032
P值		0.029	0.633		0.058	0.474	0.841	0.859
组别	基础疾病		高血压分级		脑出血部位
组别	糖尿病/ [例（%）]	高脂血症/ [例（%）]	2级/ [例（%）]	3级/ [例（%）]	基底核区/ [例（%）]	丘脑/ [例（%）]	脑室/ [例（%）]	小脑及脑干/ [例（%）]
无效组	30（63.83）	25（53.19）	11（23.40）	36（76.60）	12（25.53）	9（19.15）	8（17.02）	18（38.30）
有效组	63（60.00）	54（51.43）	76（72.38）	29（27.62）	20（19.05）	18（17.14）	21（20.00）	46（43.81）
统计值	0.201	0.04	31.818		1.107
P值	0.654	0.841	<0.001		0.775
组别	脑出血量/mL	GCS评分/分	SSS评分/分		FPG/（mmol·L^-1）	TG/（mmol·L^-1）		TC/（mmol·L^-1）
无效组	26.01±4.21	9.18±2.27	29.33±5.11		7.53±1.16	1.74±0.34		5.19±0.46
有效组	23.42±3.02	12.84±2.35	25.01±3.43		7.16±1.08	1.70±0.32		5.15±0.50
统计值	4.304	8.967	6.151		1.908	3.323		8.967
P值	<0.001	<0.001	<0.001		0.058	0.001		<0.001