急性脑梗死患者miR-184表达水平与病情严重程度及炎性因子的相关性研究

苏燕; 刘凯; 杜苑苑; 熊勃超; 梁磊; 骆嵩; 屈洪党

doi:10.16766/j.cnki.issn.1674-4152.003057

急性脑梗死患者miR-184表达水平与病情严重程度及炎性因子的相关性研究

doi: 10.16766/j.cnki.issn.1674-4152.003057

蚌埠医学院第一附属医院神经内科，安徽蚌埠 233004

基金项目:

安徽省高校自然科学基金项目 KJ2019A0364

详细信息

通讯作者:
屈洪党，E-mail：qhd820@sohu.com

中图分类号: R743.3
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出版历程
- 收稿日期: 2023-02-18
- 网络出版日期: 2023-08-28

Study on the correlation between miR-184 expression levels and disease severity, inflammatory factors in patients with acute cerebral infarction

Department of Neurology, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China

摘要

摘要: 目的探讨急性脑梗死(ACI)患者血清miR-184的表达水平与病情严重程度、梗死灶体积大小与炎性因子的相关性。方法纳入蚌埠医学院第一附属医院神经内科2021年1—12月住院的ACI患者74例, 健康体检者41例, 采用qPCR、ELISA法检测2组血清miR-184、IL-6、TNF-α、CRP表达水平并进行比较，应用Spearman相关分析研究ACI患者miR-184水平与病情严重程度及与炎性因子的相关性。结果与对照组比较，ACI组miR-184水平降低(P < 0.001), IL-6、TNF-α和CRP水平升高(均P < 0.05), 且梗死灶体积越大，NHISS评分越高，miR-184水平越低。Spearman相关性分析结果显示：ACI患者血清miR-184水平与病情严重程度、梗死灶体积呈负相关关系(r_s=-0.641、-0.620，均P < 0.05)，ACI患者血清miR-184水平与炎性因子IL-6、TNF-α、CRP水平也具有相关性(r_s=-0.560、-0.389、-0.565，均P < 0.05)。结论 miR-184与脑梗死病情严重程度、梗死灶体积及炎性因子具有相关性，miR-184可以作为诊断ACI及评估病情严重程度的血清学标志物。
- 急性脑梗死 /
- 微小RNA-184 /
- 白细胞介素-6 /
- 肿瘤坏死因子α /
- C反应蛋白
Abstract: Objective To investigate the correlation between serum miR-184 levels and severity of disease and with inflammatory factors in patients with acute cerebral infarction (ACI). Methods A total of 74 ACI patients and 41 healthy individuals were included in the Neurology Department of the First Affiliated Hospital of Bengbu Medical College from January to December 2021. The expression levels of miR-184, IL-6, TNF-α and CRP in the serum of the two groups were detected using qPCR and ELISA methods; the levels between two groups were compared, and Pearson correlation analysis was applied to study the correlation between miR-184 levels and inflammatory factors in ACI patients. Results Compared with the control group, the levels of miR-184 in the ACI group decreased (P < 0.001), while the levels of IL-6, TNF-α, and CRP increased (all P < 0.05). The larger the infarct size, the higher the NHISS score, and the lower the miR-184 level. Spearman correlation analysis showed that the level of serum miR-184 in ACI patients was negatively correlated with disease severity and infarct volume (r_s=-0.641, -0.620, both P < 0.05). The level of serum miR-184 in ACI patients was also correlated with the levels of inflammatory factors IL-6, TNF-α and CRP levels (r_s=-0.560, -0.389, -0.565, all P < 0.05). Conclusion miR-184 can be used as a serological marker for diagnosing ACI and evaluating the severity of the condition, and is a promising target for the treatment of ACI.
- Acute cerebral infarction /
- mir-184 /
- Interleukin-6 /
- Tumor necrosis factor α /
- C-reactive protein

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图 1 miR-184水平诊断ACI的ROC曲线

Figure 1. ROC curve of miR-184 level for the diagnosis of ACI

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表 1 内参U6的引物序列

Table 1. Primer sequences for reference U6

引物名称	引物序列	碱基数	PCR产物大小(bp)
Homo U6 Forward primer	CTCGCTTCGGCAGCACA(5’→3’)	17	91
Homo U6 Reverse primer	ACGCTTCACGAATTTGCG(5’→3’)	18	91

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表 2 2组研究对象一般资料比较

Table 2. Comparison of general data between the two groups

组别	例数	性别 (男性/女性，例)	年龄 (x±s，岁)	有吸烟史 [例(%)]	有饮酒史 [例(%)]	收缩压 (x±s，mmHg)	舒张压 (x±s，mmHg)	甘油三酯 (x±s，mmol/L)
ACI组	74	44/30	66.97±6.39	22(29.73)	16(21.62)	149.14±20.76	87.32±16.28	1.40±0.42
对照组	41	24/17	65.49±4.30	20(48.78)	15(36.59)	132.80±15.16	82.83±10.72	1.42±0.55
统计量		0.009^a	1.483^b	4.130^a	0.837^a	4.422^b	1.779^b	-0.230^b
P值		0.923	0.141	0.042	0.360	< 0.001	0.078	0.819

组别	例数	总胆固醇 (x±s，mmol/L)	低密度脂蛋白 (x±s，mmol/L)	高密度脂蛋白 (x±s，mmol/L)	尿酸 (x±s，μmol/L)	BMI (x±s)	空腹血糖[M(P₂₅, P₇₅)，mmol/L]
ACI组	74	4.12±0.83	2.77±0.61	1.08±0.21	328.93±74.03	25.43±2.92	6.66(5.17，8.52)
对照组	41	3.74±0.77	2.34±0.61	1.08±0.29	310.46±56.02	24.54±3.17	5.37(4.69，6.12)
统计量		2.432^b	3.612^b	-0.061^b	1.505^b	1.515^b	-3.536^c
P值		0.017	< 0.001	0.951	0.135	0.133	< 0.001
注：^a为χ²值，^b为t值, ^c为Z值。1 mmHg=0.133 kPa。

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表 3 2组血清miR-184、IL-6、TNF-α及CRP水平比较

Table 3. Comparison of serum miR-184, IL-6, TNF-α and CRP levels between the two groups

组别	例数	miR-184 [M(P₂₅, P₇₅)]	IL-6[M(P₂₅, P₇₅), pg/mL]	TNF-α (x±s, ng/mL)	CRP[M(P₂₅, P₇₅), mg/L]
ACI组	74	1.31(1.02, 2.15)	6.57(2.27, 12.04)	55.29±9.00	6.96(4.00, 13.76)
对照组	41	3.42(2.66, 3.69)	1.55(1.43, 3.04)	31.29±8.63	2.20(1.40, 3.15)
统计量		-6.239^a	-5.021^a	13.914^b	-5.958^a
P值		< 0.001	< 0.001	< 0.001	< 0.001
注：^a为Z值, ^b为t值。

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表 4 不同梗死体积ACI患者血清miR-184、IL-6、TNF-α、CRP水平比较

Table 4. Comparison of serum miR-184, IL-6, TNF-α and CRP levels in ACI patients with different infarct volumes

组别	例数	miR-184 [M(P₂₅, P₇₅)]	IL-6 [M(P₂₅, P₇₅)，pg/mL]	TNF-α (x±s，ng/mL)	CRP [M(P₂₅, P₇₅)，mg/L]
小梗死灶组	23	2.44(1.90，3.02)	2.07(1.40，5.06)	52.20±9.21	4.00(1.30, 5.43)
中梗死灶组	35	1.29(1.03，1.71)^a	6.48(4.27，8.64)^a	54.89±9.13	7.08(5.42, 10.87)^a
大梗死灶组	16	0.57(0.49，0.71)^ab	22.82(12.37，35.53)^ab	60.63±5.85^ab	21.23(15.10, 25.14)^ab
统计量		39.806^c	30.424^c	4.639^d	39.632^c
P值		< 0.001	< 0.001	0.013	< 0.001
注：与小梗死灶组比较, ^aP < 0.05；与中梗死灶组比较, ^bP < 0.05。^c为H值，^d为F值。

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表 5 不同病情严重程度ACI患者血清miR-184、IL-6、TNF-α、CRP水平比较

Table 5. Comparison of serum miR-184, IL-6, TNF-α and CRP levels in ACI patients with different disease severity

组别	例数	miR-184 [M(P₂₅, P₇₅)]	IL-6 [M(P₂₅, P₇₅)，pg/mL]	TNF-α (x±s，ng/mL)	CRP [M(P₂₅, P₇₅)，mg/L]
轻度组	27	2.30(1.90, 2.97)	2.07(1.40, 7.65)	52.86±9.70	4.00(1.30, 6.18)
中度组	29	1.24(1.03, 1.57)^a	6.48(4.42, 8.64)a	54.96±9.00	7.05(5.52, 10.42)^a
重度组	18	0.62(0.50, 1.21)^ab	21.22(11.74, 35.48)^ab	59.49±6.42^a	19.23(13.22, 24.77)^ab
统计量		42.300^c	29.073^c	3.148^d	38.477^c
P值		< 0.001	< 0.001	0.049	< 0.001
注：与轻度组比较，^aP < 0.05；与中度组比较，^bP < 0.05。^c为H值，^d为F值。

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