外周血miR-320b表达水平对颈动脉粥样硬化斑块性质的评价研究

doi:10.3877/cma.j.issn.2095-123X.2022.04.008

目的

探讨外周血miR-320b表达水平对颈动脉粥样硬化斑块性质的评价价值。

方法

选取亳州市人民医院神经内科自2020年5月至2021年9月收治的108例颈动脉粥样硬化患者设为研究组，另选取同时期的105例健康志愿者设为对照组。测定并比较2组受试者外周血miR-320b表达水平。根据颈动脉超声检查结果将研究组患者分为无斑块组和斑块组，对比miR-320b表达水平。另根据高分辨率磁共振成像检查将斑块组患者分为不稳定斑块组与稳定斑块组，对比miR-320b表达水平，分析颈动脉粥样硬化斑块性质的影响因素及miR-320b水平对颈动脉粥样硬化不稳定斑块的评价作用。

结果

研究组外周血miR-320b表达水平较对照组降低，差异有统计学意义（P<0.05）。与无斑块组相比，斑块组患者外周血miR-320b表达水平显著降低，差异有统计学意义（P<0.05）。外周血miR-320b水平评估颈动脉粥样硬化斑块的受试者工作特征（ROC）曲线结果显示，曲线下面积（AUC）为0.948，敏感度、特异度分别为88.24%、97.30%。美国心脏病协会（AHA）颈动脉斑块Ⅳ~Ⅴ型、Ⅵ型患者外周血miR-320b表达水平均低于Ⅰ~Ⅱ型、Ⅲ型、Ⅶ型、Ⅷ型患者，且Ⅵ型患者miR-320b表达水平低于Ⅳ~Ⅴ型患者，差异有统计学意义（P<0.05）。和稳定组斑块相比，不稳定斑块组外周血中的miR-320b表达水平显著降低（P<0.05）。多因素Logistic回归性分析显示，总胆固醇、低密度脂蛋白胆固醇水平均是颈动脉粥样硬化不稳定斑块的危险因素（OR=1.979、2.217，P<0.05），而高密度脂蛋白胆固醇、外周血miR-320b表达水平是其保护因素（OR=0.641、0.548，P<0.05）。外周血miR-320b表达水平评估颈动脉粥样硬化不稳定斑块的ROC结果显示，AUC为0.915，敏感度76.47%，特异度92.50%。

结论

外周血miR-320b表达水平可能和颈动脉粥样硬化斑块性质存在一定的关系，可较好地评估斑块不稳定性。

关键词: 颈动脉粥样硬化, 斑块性质, miR-320b

Objective

To investigate the value of the miR-320b expression level in peripheral blood in evaluating the nature of carotid atherosclerotic plaque.

Methods

The 108 patients with carotid atherosclerosis admitted in Neurology Department of Bozhou People’s Hospital from May 2020 to September 2021 were set as the study group, and the 105 healthy volunteers in the same period were set as the control group. The expression levels of miR-320b in peripheral blood of the 2 groups were measured and compared. The patients in the study group were divided into plaque-free group and plaque group according to the results of carotid artery ultrasound examination, and the expression level of miR-320b was compared. In addition, according to the results of high resolution magnetic resonance imaging, the patients in the plaque group were divided into unstable plaque group and stable plaque group, and the miR-320b level in the this 2 groups was compared. The influencing factors of the nature of carotid atherosclerotic plaque and the evaluation effect of miR-320b level on unstable plaque of carotid atherosclerosis were analyzed.

Results

The expression level of miR-320b in peripheral blood of the study group was lower than that of the control group (P<0.05). Compared with plaque-free group, the expression level of miR-320b in peripheral blood in the plaque group was significantly lower (P<0.05). The results of receiver operating characteristic (ROC) curve of miR-320b level in peripheral blood in evaluating carotid atherosclerotic plaque showed that the area under the curve (AUC) was 0.948, and the sensitivity and specificity were 88.24% and 97.30% respectively. The expression levels of miR-320b in peripheral blood of patients with carotid plaque type Ⅳ-Ⅴ and Ⅵ of American Heart Association (AHA) were lower than that of patients with type Ⅰ-Ⅱ, type Ⅲ, type Ⅶ and type Ⅷ, and the expression level of miR-320b in type Ⅵ patients was lower than that in type Ⅳ-Ⅴ patients, and the difference was statistically significant (P<0.05). Compared with the stable plaque group, the expression level of miR-320b in peripheral blood in the unstable plaque group was significantly lower (P<0.05). Multivariate logistic regression analysis showed that the levels of total cholesterol and low-density lipoprotein cholesterol were risk factors for unstable plaque of carotid atherosclerosis (OR=1.979, 2.217, P<0.05), but the high-density lipoprotein cholesterol and expression level of miR-320b in peripheral blood were protective factors for it (OR=0.641, 0.548, P<0.05). The ROC results of the expression level of miR-320b in peripheral blood in evaluating unstable plaques of carotid atherosclerotic showed that the AUC was 0.915, and the sensitivity and specificity were 76.47% and 92.50% respectively.

Conclusion

The expression level of miR-320b in peripheral blood may be related to the nature of carotid atherosclerotic plaque, which can better evaluate plaque instability.

Key words: Carotid atherosclerosis, Plaque property, miR-320b

表1 斑块组、无斑块组临床资料比较

临床资料		无斑块组（n=34）	斑块组（n=74）	t/χ²值	P值
年龄（岁，Mean±SD）		49.52±9.94	50.26±10.01	0.358	0.721
性别[例（%）]				0.537	0.464
	男	21（61.76）	51（68.92）
	女	13（38.24）	23（31.08）
体质量指数（kg/m²，Mean±SD）		23.02±2.36	22.58±2.29	0.919	0.360
收缩压（mmHg，Mean±SD）		135.32±30.22	136.91±30.47	0.253	0.801
舒张压（mmHg，Mean±SD）		84.90±16.95	87.62±17.52	0.757	0.451
总胆固醇（mmol/L，Mean±SD）		4.56±0.76	5.21±1.01	3.340	0.001
低密度脂蛋白胆固醇（mmol/L，Mean±SD）		3.45±0.82	4.51±0.98	5.483	<0.001
高密度脂蛋白胆固醇（mmol/L，Mean±SD）		1.52±0.32	1.38±0.27	2.359	0.020
肌酐（μmol/L，Mean±SD）		70.35±14.28	70.29±14.16	0.020	0.984
尿酸（μmol/L，Mean±SD）		375.64±45.23	386.13±48.31	1.417	0.159

表1 斑块组、无斑块组临床资料比较

临床资料		无斑块组（n=34）	斑块组（n=74）	t/χ²值	P值
年龄（岁，Mean±SD）		49.52±9.94	50.26±10.01	0.358	0.721
性别[例（%）]				0.537	0.464
	男	21（61.76）	51（68.92）
	女	13（38.24）	23（31.08）
体质量指数（kg/m²，Mean±SD）		23.02±2.36	22.58±2.29	0.919	0.360
收缩压（mmHg，Mean±SD）		135.32±30.22	136.91±30.47	0.253	0.801
舒张压（mmHg，Mean±SD）		84.90±16.95	87.62±17.52	0.757	0.451
总胆固醇（mmol/L，Mean±SD）		4.56±0.76	5.21±1.01	3.340	0.001
低密度脂蛋白胆固醇（mmol/L，Mean±SD）		3.45±0.82	4.51±0.98	5.483	<0.001
高密度脂蛋白胆固醇（mmol/L，Mean±SD）		1.52±0.32	1.38±0.27	2.359	0.020
肌酐（μmol/L，Mean±SD）		70.35±14.28	70.29±14.16	0.020	0.984
尿酸（μmol/L，Mean±SD）		375.64±45.23	386.13±48.31	1.417	0.159

图1 外周血miR-320b水平评估颈动脉粥样硬化斑块的ROC曲线

表2 不同颈动脉斑块分型患者外周血miR-320b表达水平比较

颈动脉斑块分型		例数	miR-320b
稳定斑块组
	Ⅰ~Ⅱ型	15	1.25±0.33
	Ⅲ型	12	1.18±0.29
	Ⅶ型	7	1.13±0.25
	Ⅷ型	6	1.00±0.19
不稳定斑块组
	Ⅳ~Ⅴ型	21	0.76±0.15^abcd
	Ⅵ型	13	0.65±0.12^abcde
F值			20.832
P值			<0.001

表2 不同颈动脉斑块分型患者外周血miR-320b表达水平比较

颈动脉斑块分型		例数	miR-320b
稳定斑块组
	Ⅰ~Ⅱ型	15	1.25±0.33
	Ⅲ型	12	1.18±0.29
	Ⅶ型	7	1.13±0.25
	Ⅷ型	6	1.00±0.19
不稳定斑块组
	Ⅳ~Ⅴ型	21	0.76±0.15^abcd
	Ⅵ型	13	0.65±0.12^abcde
F值			20.832
P值			<0.001

表3 稳定斑块组、不稳定斑块组患者的临床资料比较

临床资料		不稳定斑块组（n=34）	稳定斑块组（n=74）	t/χ²值	P值
年龄（岁，Mean±SD）		50.95±10.14	49.67±8.62	0.587	0.559
性别[例（%）]				1.503	0.220
	男	21（61.76）	30（75.00）
	女	13（38.24）	10（25.00）
体质量指数（kg/m²，Mean±SD）		22.84±2.31	22.36±2.18	0.918	0.361
收缩压（mmHg，Mean±SD）		137.52±30.41	136.39±28.15	0.181	0.857
舒张压（mmHg，Mean±SD）		88.39±9.65	86.97±10.21	0.611	0.543
总胆固醇（mmol/L，Mean±SD）		5.68±1.14	4.81±0.93	3.616	0.001
低密度脂蛋白胆固醇（mmol/L，Mean±SD）		4.92±0.85	4.16±0.64	4.381	<0.001
高密度脂蛋白胆固醇（mmol/L，Mean±SD）		1.19±0.23	1.54±0.28	5.809	<0.001
肌酐（μmol/L，Mean±SD）		71.85±13.85	68.94±14.28	0.886	0.379
尿酸（μmol/L，Mean±SD）		389.24±49.52	383.49±51.26	0.488	0.627

表3 稳定斑块组、不稳定斑块组患者的临床资料比较

临床资料		不稳定斑块组（n=34）	稳定斑块组（n=74）	t/χ²值	P值
年龄（岁，Mean±SD）		50.95±10.14	49.67±8.62	0.587	0.559
性别[例（%）]				1.503	0.220
	男	21（61.76）	30（75.00）
	女	13（38.24）	10（25.00）
体质量指数（kg/m²，Mean±SD）		22.84±2.31	22.36±2.18	0.918	0.361
收缩压（mmHg，Mean±SD）		137.52±30.41	136.39±28.15	0.181	0.857
舒张压（mmHg，Mean±SD）		88.39±9.65	86.97±10.21	0.611	0.543
总胆固醇（mmol/L，Mean±SD）		5.68±1.14	4.81±0.93	3.616	0.001
低密度脂蛋白胆固醇（mmol/L，Mean±SD）		4.92±0.85	4.16±0.64	4.381	<0.001
高密度脂蛋白胆固醇（mmol/L，Mean±SD）		1.19±0.23	1.54±0.28	5.809	<0.001
肌酐（μmol/L，Mean±SD）		71.85±13.85	68.94±14.28	0.886	0.379
尿酸（μmol/L，Mean±SD）		389.24±49.52	383.49±51.26	0.488	0.627

表4 颈动脉粥样硬化不稳定斑块的多因素Logistic回归分析

危险因素	β值	SE	Wald χ²值	P值	OR值	95%CI
总胆固醇	0.683	0.316	4.672	0.015	1.979	1.368~2.572
低密度脂蛋白胆固醇	0.796	0.349	5.202	0.009	2.217	1.654~2.985
高密度脂蛋白胆固醇	-0.445	0.182	5.978	0.001	0.641	0.439~0.841
外周miR-320b表达水平	-0.601	0.235	6.541	<0.001	0.548	0.316~0.768

表4 颈动脉粥样硬化不稳定斑块的多因素Logistic回归分析

危险因素	β值	SE	Wald χ²值	P值	OR值	95%CI
总胆固醇	0.683	0.316	4.672	0.015	1.979	1.368~2.572
低密度脂蛋白胆固醇	0.796	0.349	5.202	0.009	2.217	1.654~2.985
高密度脂蛋白胆固醇	-0.445	0.182	5.978	0.001	0.641	0.439~0.841
外周miR-320b表达水平	-0.601	0.235	6.541	<0.001	0.548	0.316~0.768

图2 外周血miR-320b表达水平评估颈动脉粥样硬化不稳定斑块的ROC曲线

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Evaluation of the expression level of miR-320b in peripheral blood on the nature of carotid atherosclerotic plaque

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Evaluation of the expression level of miR-320b in peripheral blood on the nature of carotid atherosclerotic plaque