血清中NSE、S100β、NT-proCNP与大鼠脓毒症相关性脑病的相关性分析
Correlation Analysis of Serum NSE, S100β, NT-proCNP and Rat Sepsis-Associated Encephalopathy
DOI: 10.12677/acm.2024.14112860, PDF,    科研立项经费支持
作者: 郑鑫寅*, 郭 倩:青岛大学医学部第四临床医学院,山东 青岛;青岛大学医学院附属烟台毓璜顶医院急诊科,山东 青岛;黄文钰, 康 海#:青岛大学医学院附属烟台毓璜顶医院急诊科,山东 青岛
关键词: 脓毒症相关性脑病神经元特异性烯醇化酶C型利钠肽及其氨基末端前肽中枢神经特异蛋白神经行为学评分肿瘤坏死因子-αSepsis Associated Encephalopathy Neuron Specific Enolase C-Type Natriuretic Peptide and Its Amino Terminal Propeptide Central Nerve Specific Protein Neurobehavioral Score Tumor Necrosis Factor-α
摘要: 目的:探讨神经元特异性烯醇化酶(NSE)、C型利钠肽及其氨基末端前肽(NT-proCNP)和中枢神经特异蛋白(S100β)与脓毒症相关性脑病(SAE)的相关性。方法:SD大鼠共计36只,随机数字表法分为两组(n = 18),即假手术组(Sham组)和脓毒症相关性脑病组(SAE组),每组分别在12 h、24 h和48 h进行神经行为学评分并取材。取大鼠心室血离心取上清液,Elisa法检测血清中肿瘤坏死因子-α (TNF-α)、NSE、NT-proCNP、S100β的水平。HE染色观察两组海马组织形态学变化。结果:与Sham组同时间相比,SAE组在24 h和48 h时行为学评分明显降低(SAE组平均数 ± 标准差vs Sham组平均数 ± 标准差,P < 0.05;SAE组平均数 ± 标准差vs Sham组平均数 ± 标准差,P < 0.05)。Elisa法结果显示,相较于Sham组,SAE组TNF-α表达在12 h、24 h和48 h均明显提高(SAE组平均数 ± 标准差vs Sham组平均数 ± 标准差,P < 0.01),SAE组NSE的表达在24 h和48 h时明显提高(SAE组平均数 ± 标准差vs Sham组平均数 ± 标准差,P < 0.05);SAE组NT-proCNP的表达在24 h和48 h时明显提高(SAE组平均数 ± 标准差vs Sham组平均数 ± 标准差,P < 0.05);SAE组S100β的表达在24 h和48 h时明显提高(SAE组平均数 ± 标准差vs Sham组平均数 ± 标准差,P < 0.05);SAE组内相较于12 h,S100β的表达在24 h和48 h时明显提高(SAE组24 h平均数 ± 标准差vs SAE组48 h平均数 ± 标准差,P < 0.01)。HE结果显示,与Sham组相比,SAE组脑区海马区域组织明显水肿,空泡状增多。结论:大鼠血清中NSE、NT-proCNP和S100β水平的升高与SAE发生具有相关性,动态监测脓毒症患者血清中水平的变化有助于早期发现和诊断SAE。
Abstract: Objective: To explore the correlation between neuron specific enolase (NSE), soluble protein-100β (S100β), amino-terminal pro-C-type natriuretic peptides (NT-proCNP) and sepsis-associated encephalopathy (SAE). Methods: A total of 36 Sprague-Dawley rats were equally distributed into two groups (n = 18), namely the Sham group (undergoing Sham surgery) and the SAE group (with sepsis-associated encephalopathy). At 12 h, 24 h, and 48 h, each group underwent neurobehavioral scoring and tissue collection. The serum was extracted from rat ventricular blood through centrifugation for subsequent measurement of tumor necrosis factor-α (TNF-α), NSE, NT-proCNP, and S100β levels using Elisa. HE staining was employed to examine the structural alterations within the hippocampal tissues of the two groups. Results: Compared with the Sham group, the SAE group showed a significant decrease in neurobehavioral score at 24 h and 48 h (SAE group mean ± SD vs Sham group mean ± SD, P < 0.05; SAE group mean ± SD vs Sham group mean ± SD, P < 0.05). Elisa results showed that compared to the Sham group, TNF-α expression in the SAE group was significantly increased at 12 h, 24 h, and 48 h (SAE group mean ± SD vs Sham group mean ± SD, P < 0.01), NSE expression in the SAE group was significantly increased at 24 h and 48 h (SAE group mean ± SD vs Sham group mean ± SD, P < 0.05); NT-proCNP expression in the SAE group was significantly increased at 24 h and 48 h (SAE group mean ± SD vs Sham group mean ± SD, P < 0.05); S100β expression in the SAE group was significantly increased at 24 h and 48 h (SAE group mean ± SD vs Sham group mean ± SD, P < 0.05); within the SAE group, compared to 12 h, S100β expression was significantly increased at 24 h and 48 h (SAE group 24 h mean ± SD vs SAE group 48 h mean ± SD, P < 0.01). HE staining results showed that compared with the Sham group, the brain region of the hippocampus in the SAE group showed obvious edema and increased vacuolation. Conclusion: The increased levels of NSE, NT-proCNP and S100β in serum of rats are correlated with the occurrence of SAE. Dynamic monitoring of serum levels in sepsis patients is helpful for early detection and diagnosis of SAE.
文章引用:郑鑫寅, 黄文钰, 康海, 郭倩. 血清中NSE、S100β、NT-proCNP与大鼠脓毒症相关性脑病的相关性分析[J]. 临床医学进展, 2024, 14(11): 160-169. https://doi.org/10.12677/acm.2024.14112860

参考文献

[1] 孙啸宇, 陆宗庆, 张金, 肖文艳, 华天凤, 杨旻. 《拯救脓毒症运动: 脓毒症与脓毒性休克治疗国际指南(2021)》摘译与解读[J]. 中国中西医结合急救杂志, 2021, 28(6): 645-652.
[2] Evans, L., Rhodes, A., Alhazzani, W., Antonelli, M., Coopersmith, C.M., French, C., et al. (2021) Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Intensive Care Medicine, 47, 1181-1247. [Google Scholar] [CrossRef] [PubMed]
[3] Dumbuya, J.S., Li, S., Liang, L. and Zeng, Q. (2023) Paediatric Sepsis-Associated Encephalopathy (SAE): A Comprehensive Review. Molecular Medicine, 29, Article No. 27. [Google Scholar] [CrossRef] [PubMed]
[4] Slooter, A.J.C., Otte, W.M., Devlin, J.W., Arora, R.C., Bleck, T.P., Claassen, J., et al. (2020) Updated Nomenclature of Delirium and Acute Encephalopathy: Statement of Ten Societies. Intensive Care Medicine, 46, 1020-1022. [Google Scholar] [CrossRef] [PubMed]
[5] 黄义洲, 耿晓娟, 赵文静. 脓毒症所致脑功能障碍的研究进展[J]. 临床麻醉学杂志, 2020, 36(7): 708-711.
[6] Chaudhry, N. and Duggal, A.K. (2014) Sepsis Associated Encephalopathy. Advances in Medicine, 2014, Article ID: 762320. [Google Scholar] [CrossRef] [PubMed]
[7] Yang, L., Li, Z., Xu, Z., Zhang, B., Liu, A., He, Q., et al. (2022) Protective Effects of Cannabinoid Type 2 Receptor Activation against Microglia Overactivation and Neuronal Pyroptosis in Sepsis-Associated Encephalopathy. Neuroscience, 493, 99-108. [Google Scholar] [CrossRef] [PubMed]
[8] Ferrete-Araujo, A.M., Rodríguez-Rodríguez, A., Egea-Guerrero, J.J., Vilches-Arenas, Á., Godoy, D.A. and Murillo-Cabezas, F. (2019) Brain Injury Biomarker Behavior in Spontaneous Intracerebral Hemorrhage. World Neurosurgery, 132, e496-e505. [Google Scholar] [CrossRef] [PubMed]
[9] Wu, X., Yan, T., Wang, Z., Dong, X., Yu, W., Zheng, Y., et al. (2022) Role of Plasma Apo-J as a Biomarker of Severity and Outcome after Intracerebral Hemorrhage: A Prospective and Cohort Study. Clinica Chimica Acta, 533, 148-155. [Google Scholar] [CrossRef] [PubMed]
[10] Hu, Q., Wu, X., Wang, Z., Yan, T., Wang, L., Yu, W., et al. (2023) α-MSH as a Potential Biomarker of Severity and Prognosis after Intracerebral Hemorrhage: A Prospective Cohort Study. Clinica Chimica Acta, 538, 131-138. [Google Scholar] [CrossRef] [PubMed]
[11] Kishore, J., Shaikh, F., Zubairi, A.M., Mirza, S., Alqutub, M.N., AlMubarak, A.M., et al. (2021) Evaluation of Serum Neuron Specific Enolase Levels among Patients with Primary and Secondary Burning Mouth Syndrome. Cephalalgia, 42, 119-127. [Google Scholar] [CrossRef] [PubMed]
[12] Ye, W., Tang, Y., Dong, X., Chen, G., Yan, Y., Zhou, L., et al. (2020) Predictive Value and Correlation of Neuron-Specific Enolase for Prognosis in Patients with Coma: A Systematic Review and Meta-Analysis. European Neurology, 83, 555-565. [Google Scholar] [CrossRef] [PubMed]
[13] He, Y., Cai, Z. and Chen, Y. (2018) Role of S-100β in Stroke. International Journal of Neuroscience, 128, 1180-1187. [Google Scholar] [CrossRef] [PubMed]
[14] Tomasiuk, R. (2022) N-terminal Pro-C-Type Natriuretic Peptide: The Novel Marker in Selected Disease Units. Protein & Peptide Letters, 29, 125-132. [Google Scholar] [CrossRef] [PubMed]
[15] Mazeraud, A., Righy, C., Bouchereau, E., Benghanem, S., Bozza, F.A. and Sharshar, T. (2020) Septic-associated Encephalopathy: A Comprehensive Review. Neurotherapeutics, 17, 392-403. [Google Scholar] [CrossRef] [PubMed]
[16] Hu, J., Xie, S., Xia, W., Huang, F., Xu, B., Zuo, Z., et al. (2024) Meta-Analysis of Evaluating Neuron Specific Enolase as a Serum Biomarker for Sepsis-Associated Encephalopathy. International Immunopharmacology, 131, Article ID: 111857. [Google Scholar] [CrossRef] [PubMed]
[17] Ehler, J., Saller, T., Wittstock, M., Rommer, P.S., Chappell, D., Zwissler, B., et al. (2019) Diagnostic Value of NT-ProCNP Compared to NSE and S100B in Cerebrospinal Fluid and Plasma of Patients with Sepsis-Associated Encephalopathy. Neuroscience Letters, 692, 167-173. [Google Scholar] [CrossRef] [PubMed]
[18] Chen, Z., Jalabi, W., Shpargel, K.B., Farabaugh, K.T., Dutta, R., Yin, X., et al. (2012) Lipopolysaccharide-Induced Microglial Activation and Neuroprotection against Experimental Brain Injury Is Independent of Hematogenous TLR4. The Journal of Neuroscience, 32, 11706-11715. [Google Scholar] [CrossRef] [PubMed]
[19] 张丽娜, 艾宇航, 郭曲练, 姚波, 刘志勇, 黄立, 彭倩宜. 脓毒症相关性脑病大鼠动物模型的建立[J]. 中华急诊医学杂志, 2013, 22(7): 731-736.
[20] Qin, M., Gao, Y., Guo, S., Lu, X., Zhao, Q., Ge, Z., et al. (2023) Establishment and Evaluation of Animal Models of Sepsis-Associated Encephalopathy. World Journal of Emergency Medicine, 14, 349-353. [Google Scholar] [CrossRef] [PubMed]
[21] Gao, Y., Duan, J., Ji, H. and Lu, W. (2021) Levels of S100 Calcium Binding Protein B (S100B), Neuron-Specific Enolase (NSE), and Cyclophilin a (CypA) in the Serum of Patients with Severe Craniocerebral Injury and Multiple Injuries Combined with Delirium Transferred from the ICU and Their Prognostic Value. Annals of Palliative Medicine, 10, 3371-3378. [Google Scholar] [CrossRef] [PubMed]
[22] Luescher, T., Mueller, J., Isenschmid, C., Kalt, J., Rasiah, R., Tondorf, T., et al. (2019) Neuron-Specific Enolase (NSE) Improves Clinical Risk Scores for Prediction of Neurological Outcome and Death in Cardiac Arrest Patients: Results from a Prospective Trial. Resuscitation, 142, 50-60. [Google Scholar] [CrossRef] [PubMed]
[23] Nolan, J.P., Sandroni, C., Böttiger, B.W., Cariou, A., Cronberg, T., Friberg, H., et al. (2021) European Resuscitation Council and European Society of Intensive Care Medicine Guidelines 2021: Post-Resuscitation Care. Intensive Care Medicine, 47, 369-421. [Google Scholar] [CrossRef] [PubMed]
[24] Eckerström, M., Nilsson, S., Zetterberg, H., Blennow, K. and Grahn, A. (2020) Cognitive Impairment without Altered Levels of Cerebrospinal Fluid Biomarkers in Patients with Encephalitis Caused by Varicella-Zoster Virus: A Pilot Study. Scientific Reports, 10, Article No. 22400. [Google Scholar] [CrossRef] [PubMed]
[25] Bloomfield, S.M., McKinney, J., Smith, L. and Brisman, J. (2007) Reliability of S100B in Predicting Severity of Central Nervous System Injury. Neurocritical Care, 6, 121-138. [Google Scholar] [CrossRef] [PubMed]
[26] Jacob, J., Chopra, S., Cherian, D. and Verghese, P. (2013) Physiology and Clinical Significance of Natriuretic Hormones. Indian Journal of Endocrinology and Metabolism, 17, 83-90. [Google Scholar] [CrossRef] [PubMed]