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)

全文 ( ) 下载PDF ( ) 导出引用

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/OL]. 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/OL]. 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

[1]	Wang SS, Yang Y, Velz J, et al. Management of brainstem haemorrhages[J]. Swiss Med Wkly, 2019, 149: w20062. DOI: 10.4414/smw.2019.20062.
[2]	Arseni C, Staneiu M. Primary haematomas of the brain stem[J]. Acta Neurochir (Wien), 1973, 28(4): 323-330. DOI: 10.1007/bf01405650.
[3]	Hemphill JC, 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American heart association/American stroke association[J]. Stroke, 2015, 46(7): 2032-2060. DOI: 10.1161/str.0000000000000069.
[4]	Chen P, Yao H, Tang X, et al. Management of primary brainstem hemorrhage: a review of outcome prediction, surgical treatment, and animal model[J]. Dis Markers, 2022, 2022: 4293590. DOI: 10.1155/2022/4293590.
[5]	Chen LH, Li FJ, Zhang HT, et al. The microsurgical treatment for primary hypertensive brainstem hemorrhage: experience with 52 patients[J]. Asian J Surg, 2021, 44(1): 123-130. DOI: 10.1016/j.asjsur.2020.04.016.
[6]	Wang Q, Guo W, Liu Y, et al. Application of a 3D-printed navigation mold in puncture drainage for brainstem hemorrhage[J]. J Surg Res, 2020, 245: 99-106. DOI: 10.1016/j.jss.2019.07.026.
[7]	Barletta JF, Bruno JJ, Buckley MS, et al. Stress ulcer prophylaxis[J]. Crit Care Med, 2016, 44(7): 1395-1405. DOI: 10.1097/ccm.0000000000001872.
[8]	Burucoa C, Axon A. Epidemiology of helicobacter pylori infection[J]. Helicobacter, 2017, 22 Suppl 1: 1-5. DOI: 10.1111/hel.12403.
[9]	Costable NJ, Greenwald DA. Upper gastrointestinal bleeding[J]. Clin Geriatr Med, 2021, 37(1): 155-172. DOI: 10.1016/j.cger.2020.09.001.
[10]	Lanas A, Dumonceau JM, Hunt RH, et al. Non-variceal upper gastrointestinal bleeding[J]. Nat Rev Dis Primers, 2018, 4: 18020. DOI: 10.1038/nrdp.2018.20.
[11]	Robert R, Gissot V, Pierrot M, et al. Helicobacter pylori infection is not associated with an increased hemorrhagic risk in patients in the intensive care unit[J]. Crit Care, 2006, 10(3): R77. DOI: 10.1186/cc4920.
[12]	Satoh K, Yoshino J, Akamatsu T, et al. Evidence-based clinical practice guidelines for peptic ulcer disease 2015[J]. J Gastroenterol, 2016, 51(3): 177-194. DOI: 10.1007/s00535-016-1166-4.
[13]	Zhao J, Li X, Hu J, et al. Mesenchymal stromal cell-derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization[J]. Cardiovasc Res, 2019, 115(7): 1205-1216. DOI: 10.1093/cvr/cvz040.
[14]	Wu M, Zhang Y. MiR-182 inhibits proliferation, migration, invasion and inflammation of endometrial stromal cells through deactivation of NF-κB signaling pathway in endometriosis[J]. Mol Cell Biochem, 2021, 476(3): 1575-1588. DOI: 10.1007/s11010-020-03986-2.
[15]	Ibáñez F, Montesinos J, Ureña-Peralta JR, et al. TLR4 participates in the transmission of ethanol-induced neuroinflammation via astrocyte-derived extracellular vesicles[J]. J Neuroinflammation, 2019, 16(1): 136. DOI: 10.1186/s12974-019-1529-x.
[16]	Wang Z, Zhang M, Wang Z, et al. Cyanidin-3-O-glucoside attenuates endothelial cell dysfunction by modulating miR-204-5p/SIRT1-mediated inflammation and apoptosis[J]. Biofactors, 2020, 46(5): 803-812. DOI: 10.1002/biof.1660.
[17]	Liu B, Liu S, Yin A, et al. Risks and benefits of stress ulcer prophylaxis in adult neurocritical care patients: a systematic review and meta-analysis of randomized controlled trials[J]. Crit Care, 2015, 19: 409. DOI: 10.1186/s13054-015-1107-2.
[18]	Isik M, Ozbayer C, Donmez DB, et al. Effects of the probiotic, Lactobacillus rhamnosus GG, on ulcer pathogenesis, HSP70 stress protein and nitric oxide levels in stress induced ulcer[J]. Biotech Histochem, 2022, 97(6): 449-460. DOI: 10.1080/10520295.2022.2028308.
[19]	Wijaya D, Suharjono, Matulatan F, et al. Analysis of stress ulcer prophylaxis drug regimentation in surgical patients[J]. J Basic Clin Physiol Pharmacol, 2021, 32(4): 645-649. DOI: 10.1515/jbcpp-2020-0428.
[20]	Nagy P, Johansson S, Molloy-Bland M. Systematic review of time trends in the prevalence of helicobacter pylori infection in China and the USA[J]. Gut Pathog, 2016, 8: 8. DOI: 10.1186/s13099-016-0091-7.
[21]	Szkaradkiewicz A, Karpiński TM, Linke K, et al. Expression of cagA, virB/D Complex and/or vacA genes in helicobacter pylori strains originating from patients with gastric diseases[J]. PLoS One, 2016, 11(2): e0148936. DOI: 10.1371/journal.pone.0148936.
[22]	Ansari S, Yamaoka Y. Role of vacuolating cytotoxin A in helicobacter pylori infection and its impact on gastric pathogenesis[J]. Expert Rev Anti Infect Ther, 2020, 18(10): 987-996. DOI: 10.1080/14787210.2020.1782739.
[23]	Nell S, Estibariz I, Krebes J, et al. Genome and methylome variation in helicobacter pylori with a cag pathogenicity island during early stages of human infection[J]. Gastroenterology, 2018, 154(3): 612-623.e7. DOI: 10.1053/j.gastro.2017.10.014.
[24]	Mentis A, Lehours P, Mégraud F. Epidemiology and diagnosis of helicobacter pylori infection[J]. Helicobacter, 2015, 20 Suppl 1: 1-7. DOI: 10.1111/hel.12250.
[25]	Vaira D. Changing prevalence of helicobacter pylori infection and peptic ulcer among dyspeptic patients[J]. Intern Emerg Med, 2015, 10(7): 763-764. DOI: 10.1007/s11739-015-1296-3.
[26]	Flores-Pérez A, Marchat LA, Rodríguez-Cuevas S, et al. Dual targeting of ANGPT1 and TGFBR2 genes by miR-204 controls angiogenesis in breast cancer[J]. Sci Rep, 2016, 6: 34504. DOI: 10.1038/srep34504.

[1]	杨桂清, 孟静静. 哺乳期亚临床乳腺炎的研究进展[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 376-379.
[2]	吕军好, 林锦雯, 张心怡, 陈江华. 细胞外囊泡在肾移植诊断和治疗中的研究进展[J/OL]. 中华移植杂志(电子版), 2024, 18(03): 186-192.
[3]	刘中文, 刘畅, 高洋, 刘东, 林世庆, 杨建华, 赵福义. 尿液microRNA-326与腹腔镜根治性膀胱切除术治疗膀胱癌患者预后的相关性研究[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(04): 386-391.
[4]	黄海, 程必盛, 黄健. 2024年欧洲泌尿外科学会年会：前列腺癌研究的前沿探索与未来趋势[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(03): 202-207.
[5]	甘志新, 胡雍军, 肖晶, 胡明冬. 降钙素原在脓毒血症与肺部感染中的研究进展[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(04): 663-666.
[6]	季鹏程, 鄂一民, 陆晨, 喻春钊. 循环外泌体相关生物标志物在结直肠癌诊断中的研究进展[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(04): 265-273.
[7]	冯熔熔, 苏晓乐, 王利华. 慢性肾脏病患者并发心血管疾病相关生物标志物研究进展[J/OL]. 中华肾病研究电子杂志, 2024, 13(05): 273-278.
[8]	张晓青, 唐雯. 基于临床化验指标重新计算的生物标记物在预测腹膜透析患者预后中的作用研究进展[J/OL]. 中华肾病研究电子杂志, 2024, 13(04): 213-218.
[9]	张轶男, 朱国贞. 急性肾损伤向慢性肾脏病转变研究进展[J/OL]. 中华肾病研究电子杂志, 2024, 13(02): 106-112.
[10]	潘冬生, 梁国标. 颅脑创伤治疗的最新进展与未来趋势[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(04): 193-197.
[11]	王江波, 尹一鸣, 张冠群. 外周血生物标志物在阿尔茨海默病早期诊断中的价值[J/OL]. 中华脑科疾病与康复杂志(电子版), 2024, 14(04): 244-249.
[12]	柏明涛, 黄宝辰, 牛纪杰, 张玉海, 穆振欣. 原发性脑干出血30天死亡的危险因素分析[J/OL]. 中华脑科疾病与康复杂志(电子版), 2024, 14(04): 213-217.
[13]	王燕, 梁海乾, 郭姗姗. 炎症小体在创伤性脑损伤中作用的研究进展[J/OL]. 中华脑科疾病与康复杂志(电子版), 2024, 14(03): 177-181.
[14]	武文晓, 张大奎, 孙志刚, 韩子翰, 陈少轩, 侯智勇, 孙白龙, 介建政. pMMR/MSS型结肠癌免疫治疗效果及预后标志物研究[J/OL]. 中华临床医师杂志(电子版), 2024, 18(01): 41-56.
[15]	黄镪, 孙金梅, 韩燕飞, 张拥波. 脑源性与非脑源性疾病所致应激性溃疡相关胃肠道出血的影响因素及临床预后差异：一项回顾性队列研究[J/OL]. 中华脑血管病杂志(电子版), 2024, 18(04): 309-316.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

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

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

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