幽门螺杆菌感染和循环miRNA变化与老年脑干出血患者应激性溃疡的关系

doi:10.3877/cma.j.issn.2095-9141.2024.01.007

中华神经创伤外科电子杂志 ›› 2024, Vol. 10 ›› Issue (01) : 42 -47. doi: 10.3877/cma.j.issn.2095-9141.2024.01.007

短篇论著

幽门螺杆菌感染和循环miRNA变化与老年脑干出血患者应激性溃疡的关系

伍宵¹, 潘立², 谢理政², 茆翔²^,^†(

)

^1. 230031　合肥，安徽医科大学第一附属医院急诊科
^2. 230031　合肥，安徽医科大学第一附属医院神经外科

收稿日期:2023-03-05 出版日期:2024-02-15
通信作者: 茆翔

Relationship between Helicobacter pylori infection with circulating miRNA changes and stress ulcers in elderly patients with primary brainstem hemorrhage

Xiao Wu¹, Li Pan², Lizheng Xie², Xiang Mao²^,^†()

^1. Department of Emergency, The First Affiliated Hospital of Anhui Medical University, Hefei 230031, China
^2. Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230031, China

Received:2023-03-05 Published:2024-02-15
Corresponding author: Xiang Mao
Supported by:
Beijing Postdoctoral Fund(2020-ZZ-008); Key Project of Natural Science in Anhui Province Universities(KJ2020A0172); Anhui Province Innovation and Entrepreneurship Support Program for Returned Overseas Students(2020LCX016); Anhui Medical University Basic and Clinical Collaborative Research Enhancement Program(2022xkjT032)

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引用本文：

伍宵, 潘立, 谢理政, 茆翔. 幽门螺杆菌感染和循环miRNA变化与老年脑干出血患者应激性溃疡的关系[J]. 中华神经创伤外科电子杂志, 2024, 10(01): 42-47.

Xiao Wu, Li Pan, Lizheng Xie, Xiang Mao. Relationship between Helicobacter pylori infection with circulating miRNA changes and stress ulcers in elderly patients with primary brainstem hemorrhage[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2024, 10(01): 42-47.

目的

分析幽门螺杆菌（H. pylori）感染与老年原发性脑干出血（PBSH）患者应激性溃疡的关系，并探究血清中肿瘤坏死因子-α（TNF-α）、基质金属蛋白酶-9（MMP-9）、miR-204和miR-182对老年PBSH患者继发应激性溃疡的预测价值。

方法

回顾性分析安徽医科大学第一附属医院神经外科自2019年6月至2021年3月收治的老年PBSH患者的临床资料，根据PBSH患者胃液隐血（OB）结果将患者分为应激性溃疡组与非应激性溃疡组；根据患者血清H. pylori尿素酶抗体结果将患者分为H. pylori阳性组与H. pylori阴性组。采用双抗体夹心酶联免疫吸附试验分析血清中TNF-α和MMP-9水平，使用荧光定量PCR技术检测血清miR-204和miR-182水平，采用胶体金法检测血清H. pylori尿素酶抗体，使用OB金凝胶条检测胃液OB。采用受试者工作特征（ROC）曲线分析TNF-α、MMP-9、miR-204和miR-182水平对老年PBSH患者继发应激性溃疡的预测价值。

结果

与非应激性溃疡组相比，应激性溃疡组H. pylori阳性率显著增加，血清TNF-α、MMP-9 miR-204和miR-182含量也显著增加，差异有统计学意义（P<0.05）。与H. pylori阴性组相比，H. pylori阳性组应激性溃疡发病率（OB阳性率）显著提高，血清TNF-α、MMP-9、miR-204和miR-182含量也显著增加，差异均有统计学意义（P<0.05）。ROC曲线分析结果显示，miR-204预测应激性溃疡表现出最高的敏感性（100%），TNF-α和MMP-9表现出最高的特异性（100%）；miR-204预测H. pylori感染表现出最高的敏感性（100%），TNF-α和MMP-9表现出最高的特异性（90%）。

结论

H. pylori与老年PBSH患者应激性溃疡出血显著相关，TNF-α、MMP-9和miR-204可能是PBSH进展的新的潜在生物标志物。

关键词: 原发性脑干出血, 幽门螺杆菌感染, 应激性溃疡, 生物标志物

Objective

To analyze the relationship between Helicobacter pylori (H. pylori) infection and stress ulcers in elderly patients with primary brainstem hemorrhage (PBSH), and to explore the predictive value of serum tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), miR-204, and miR-182 for secondary stress ulcers in elderly PBSH patients.

Methods

A retrospective analysis was conducted on the clinical data of elderly PBSH patients admitted to Neurosurgery Department of the First Affiliated Hospital of Anhui Medical University from June 2019 to March 2021. Based on the results of gastric occult blood (OB) in PBSH patients, they were divided into stress ulcer group and non stress ulcer group; According to the results of the patient's serum H. pylori urease antibody, they were divided into H. pylori positive group and H. pylori negative group. The levels of TNF-α and MMP-9 in serum were analyzed by dual antibody sandwich enzyme-linked immunosorbent assay; miR-204 and miR-182 levels were detected by fluorescence quantitative PCR; serum H. pylori urease antibody was detected by colloidal gold method, and gastric juice OB was detected by OB gold gel strip. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of TNF-α, MMP-9, miR-204 and miR-182 levels for secondary stress ulcers in elderly PBSH patients.

Results

Compared with the non stress ulcer group, the positive rate of H. pylori was significantly increased in the stress ulcer group, and serum TNF-α, MMP-9, miR-204 and miR-182 was also significantly increased (P<0.05). Compared with the H. pylori negative group, the incidence rate of stress ulcer (OB positive rate) in the H. pylori positive group was significantly increased, and the serum TNF-α, MMP-9, miR-204 and miR-182 was also significantly increased (P<0.05). The ROC curve analysis results showed that miR-204 showed the highest sensitivity (100%) in predicting stress ulcers, while TNF-α and MMP-9 showed the highest specificity (100%); miR-204 showed the highest sensitivity (100%) in predicting H. pylori infection, while TNF-α and MMP-9 showd the highest specificity (90%).

Conclusion

H. pylori is significantly associated with stress ulcer bleeding in elderly PBSH patients, TNF-α, MMP-9 and miR-204 may be new potential biomarkers for the progression of PBSH.

Key words: Primary brainstem hemorrhage, Helicobacter pylori infection, Stress ulcer, Biomarker

表1 应激性溃疡组与非应激性溃疡组的一般资料对比

Tab.1 Comparison of general information between stress ulcer group and non stress ulcer group

项目	应激性溃疡组（n=19）	非应激性溃疡组（n=6）	t值	P值
年龄（岁，±s）	73.26±6.22	75.00±8.99	-0.536	0.597
性别（男）	14	5		0.629
H. pylori感染（阳性）	15	0		<0.001
血型（A/B/AB/O）				0.194
A	8	2
B	4	0
AB	0	1
O	7	3
TNF-α（pg/mL，±s）	358.00±75.14	165.00±27.14	6.091	<0.001
MMP-9（μg/L，±s）	279.74±73.49	143.83±32.62	4.346	<0.001
miR-204（±s）	5.29±0.91	3.85±1.05	3.272	0.003
miR-182（±s）	5.10±0.96	3.78±1.18	2.770	0.011

表1 应激性溃疡组与非应激性溃疡组的一般资料对比

Tab.1 Comparison of general information between stress ulcer group and non stress ulcer group

项目	应激性溃疡组（n=19）	非应激性溃疡组（n=6）	t值	P值
年龄（岁，±s）	73.26±6.22	75.00±8.99	-0.536	0.597
性别（男）	14	5		0.629
H. pylori感染（阳性）	15	0		<0.001
血型（A/B/AB/O）				0.194
A	8	2
B	4	0
AB	0	1
O	7	3
TNF-α（pg/mL，±s）	358.00±75.14	165.00±27.14	6.091	<0.001
MMP-9（μg/L，±s）	279.74±73.49	143.83±32.62	4.346	<0.001
miR-204（±s）	5.29±0.91	3.85±1.05	3.272	0.003
miR-182（±s）	5.10±0.96	3.78±1.18	2.770	0.011

表2 H. pylori阳性组与H. pylori阴性组的一般资料对比

Tab.2 Comparison of general information between H. pylori positive group and H. pylori negative group

项目	H. pylori阳性组（n=15）	H. pylori阴性组（n=10）	t值	P值
年龄（岁，±s）	72.20±5.697	75.90±8.006	-1.353	0.189
性别（男性）	12	7		0.566
OB（阳性）	15	4		0.001
血型				0.555
A	7	3
B	2	2
AB	0	1
O	6	4
TNF-α（pg/mL，±s）	380.00±57.198	209.20±77.693	6.341	<0.001
MMP-9（μg/L，±s）	301.27±62.734	165.90±49.127	5.737	<0.001
miR-204（±s）	5.51±0.882	4.11±0.905	3.840	0.001
miR-182（±s）	5.31±0.828	4.00±1.143	3.322	0.003

表2 H. pylori阳性组与H. pylori阴性组的一般资料对比

Tab.2 Comparison of general information between H. pylori positive group and H. pylori negative group

项目	H. pylori阳性组（n=15）	H. pylori阴性组（n=10）	t值	P值
年龄（岁，±s）	72.20±5.697	75.90±8.006	-1.353	0.189
性别（男性）	12	7		0.566
OB（阳性）	15	4		0.001
血型				0.555
A	7	3
B	2	2
AB	0	1
O	6	4
TNF-α（pg/mL，±s）	380.00±57.198	209.20±77.693	6.341	<0.001
MMP-9（μg/L，±s）	301.27±62.734	165.90±49.127	5.737	<0.001
miR-204（±s）	5.51±0.882	4.11±0.905	3.840	0.001
miR-182（±s）	5.31±0.828	4.00±1.143	3.322	0.003

图1 TNF-α、MMP-9、miR-204和miR-182预测应激性溃疡的ROC曲线

Fig.1 ROC curve of TNF-α, MMP-9, miR-204, and miR-182 predict the stress ulcers

图2 TNF-α、MMP-9、miR-204和miR-182预测H. pylori感染的ROC曲线

Fig.2 ROC curve of TNF-α, MMP-9, miR-204, and miR-182 predict the H. pylori infection

表3 TNF-α、MMP-9、miR-204和miR-182预测应激性溃疡的ROC曲线分析

Tab.3 ROC curve analysis of TNF-α, MMP-9, miR-204, and miR-182 predict the stress ulcers

项目	最佳截断值	灵敏度（%）	特异性（%）	AUC	95%CI
TNF-α	236	94.7	100	0.974	0.916~1.000
MMP-9	212	78.9	100	0.952	0.871~1.000
miR-204	3.84	100	66.7	0.846	0.622~1.000
miR-182	4.75	68.4	83.3	0.811	0.603~1.000

表3 TNF-α、MMP-9、miR-204和miR-182预测应激性溃疡的ROC曲线分析

Tab.3 ROC curve analysis of TNF-α, MMP-9, miR-204, and miR-182 predict the stress ulcers

项目	最佳截断值	灵敏度（%）	特异性（%）	AUC	95%CI
TNF-α	236	94.7	100	0.974	0.916~1.000
MMP-9	212	78.9	100	0.952	0.871~1.000
miR-204	3.84	100	66.7	0.846	0.622~1.000
miR-182	4.75	68.4	83.3	0.811	0.603~1.000

表4 TNF-α、MMP-9、miR-204和miR-182预测H. pylori感染的ROC曲线分析

Tab.4 ROC curve analysis of TNF-α, MMP-9, miR-204, and miR-182 predict the H. pylori infection

项目	最佳截断值	灵敏度（%）	特异性（%）	AUC	95%CI
TNF-α	297	100	90	0.960	0.878~1.000
MMP-9	212	93.3	90	0.963	0.892~1.000
miR-204	4.85	86.7	80	0.850	0.691~1.000
miR-182	4.00	93.3	60	0.813	0.637~0.990

表4 TNF-α、MMP-9、miR-204和miR-182预测H. pylori感染的ROC曲线分析

Tab.4 ROC curve analysis of TNF-α, MMP-9, miR-204, and miR-182 predict the H. pylori infection

项目	最佳截断值	灵敏度（%）	特异性（%）	AUC	95%CI
TNF-α	297	100	90	0.960	0.878~1.000
MMP-9	212	93.3	90	0.963	0.892~1.000
miR-204	4.85	86.7	80	0.850	0.691~1.000
miR-182	4.00	93.3	60	0.813	0.637~0.990

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Relationship between Helicobacter pylori infection with circulating miRNA changes and stress ulcers in elderly patients with primary brainstem hemorrhage

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Relationship between Helicobacter pylori infection with circulating miRNA changes and stress ulcers in elderly patients with primary brainstem hemorrhage