胸腺肽α1对脓毒症患者T淋巴细胞及TLR9信号通路的影响

李远思; 程玲; 张琦; 聂卫群; 林燕林

doi:10.16766/j.cnki.issn.1674-4152.002088

胸腺肽α1对脓毒症患者T淋巴细胞及TLR9信号通路的影响

doi: 10.16766/j.cnki.issn.1674-4152.002088

李远思¹,
程玲¹,
张琦^{2, 3, ,},
聂卫群¹,
林燕林¹

1.
安徽中医药大学第一附属医院重症医学科，安徽合肥 230031
2.
安徽中医药大学第一附属医院普外科，安徽合肥 230031
3.
安徽省中医药科学院外科研究所，安徽合肥 230031

基金项目:

安徽省高校优秀青年人才支持计划项目 gxyq2019035

详细信息

通讯作者:
张琦，E-mail：915443353@qq.com

中图分类号: R631 R331.144
计量
- 文章访问数: 213
- HTML全文浏览量: 113
- PDF下载量: 2
- 被引次数: 0
出版历程
- 收稿日期: 2020-09-25
- 网络出版日期: 2022-02-15

Effect of thymosin α 1 on T lymphocytes and TLR9 signaling pathway in patients with sepsis

1.
Department of Intensive Medicine, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, China

摘要

摘要: 目的通过观察胸腺肽α1治疗脓毒症患者免疫等指标的变化，为其治疗脓毒症提供依据。方法选取2017年1月—2020年8月期间安徽中医药大学第一附属医院ICU收治的50例脓毒症患者，按照随机数字表法分为对照组和观察组，各25例。对照组给予抗感染、改善脏器功能等常规综合治疗，观察组在对照组治疗的基础上加用胸腺肽α1治疗，疗程为7 d。分别观察2组患者治疗前后CD3⁺、CD8⁺、CD4⁺/CD8⁺比值等T细胞指标；降钙素原(PCT)、C反应蛋白(CRP)水平和TLR9信号通路中Toll样受体9(TLR9)、核因子KB(NF-κB)蛋白表达等炎症指标；序贯器官功能衰竭评估(SOFA)和急性生理与慢性健康状况评估Ⅱ(APACHEⅡ)评分等病情严重程度指标。结果观察组治疗后CD3⁺上升、CD8⁺下降、CD4⁺/CD8⁺比值上升，与对照组治疗后相比，差异有统计学意义(t=4.874、3.864、2.162，均P < 0.05)。观察组治疗后，患者PCT、CRP水平和TLR9、NF-κB蛋白表达水平明显低于对照组(t=4.833、7.081、5.871、8.361，均P < 0.05)。观察组治疗后SOFA和APACHEⅡ评分均下降，下降程度明显低于对照组(t=3.672、5.354，均P < 0.05)。结论胸腺肽α1可很好地调节脓毒症患者的免疫功能，减轻脓毒症的炎症反应。
- 胸腺肽α1 /
- 脓毒症 /
- T细胞亚群 /
- Toll样受体9 /
- 免疫功能
Abstract: Objective To observe the effects of thymosin α1 on changes in indicators such as immunity in patients with sepsis, and to seek evidence-based evidence for its application in the treatment of sepsis. Methods According to the random number table, 50 patients with sepsis admitted to the ICU of the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2017 to August 2020 were divided into control group and observation group with 25 cases in each group. Patients in the control group were given conventional comprehensive treatments such as anti-infection, improvement of organ function for 7 days. Patients in the observation group were treated with thymosin α1 on the basis of the conventional comprehensive treatments for 7 days. The T cell indicators such as the T cell subsets CD3⁺, CD8⁺, CD4⁺/CD8⁺ ratio before and after treatment in the two groups, inflammation indicators procalcitonin(PCT), C reactive protein(CRP) levels and TLR9, NF-κB protein expression in the TLR9 signaling pathway, disease severity indicators sequential organ failure assessment (SOFA) score and acute Physiology and chronic health evaluation (APACHE Ⅱ) score were observed. Results After treatment in the observation group, CD3⁺ increased, CD8⁺ decreased, and CD4⁺/CD8⁺ ratio increased. Compared with the control group, the difference was statistically significant (t=4.874, 3.864, 2.162, all P < 0.05). Compared with the control group, the inflammatory index PCT, CRP levels and the TLR9 and NF-KB protein expression levels in the observation group were significantly lower than those in the control group (t=4.833, 7.081, 5.871, 8.361, all P < 0.05). The disease severity indicators SOFA score and APACHE Ⅱ score decreased significantly. The SOFA score and APACHE Ⅱ score of the observation group decreased after treatment, and the degree of decline was significantly lower than that of the control group (t=3.672, 5.354, all P < 0.05). Conclusion Thymosin α1 can well regulate the immune function of patients with sepsis and reduce the inflammatory response of sepsis.
- Thymosin α1 /
- Sepsis /
- T cell subsets /
- TLR9 /
- Immune function

HTML全文

表 1 2组脓毒症患者临床基线资料比较

组别	例数	性别(男/女，例)	年龄(x±s，岁)	原发感染部位(例)
组别	例数	性别(男/女，例)	年龄(x±s，岁)	肺部	腹腔	泌尿系统	其他
观察组	25	15/10	61.2±17.1	20	3	1	1
对照组	25	13/12	60.7±16.9	19	4	1	1
统计量		0.328^a	0.104^b	0.168^a
P值		0.569	0.918	0.983
注：^a为χ²值，^b为t值。

下载: 导出CSV

表 2 2组脓毒症患者治疗前后T细胞亚群比较(x±s)

组别	例数	CD3⁺(%)		CD8⁺(%)		CD4⁺/CD8⁺
组别	例数	治疗前	治疗1周后	治疗前	治疗1周后	治疗前	治疗1周后
观察组	25	50.36±9.19	59.81±9.89^a	26.71±4.21	21.03±3.92^a	1.16±0.38	1.67±0.49^a
对照组	25	50.49±9.25	49.98±8.91	26.82±4.53	25.96±4.18	1.15±0.36	1.17±0.39^a
t值		0.561	4.874	0.173	3.864	0.121	2.162
P值		0.732	0.023	0.622	0.013	0.713	0.001
注：与同组治疗前比较，^aP＜0.05。

下载: 导出CSV

表 3 2组脓毒症患者治疗前后炎症反应指标比较(x±s)

组别	例数	PCT/(ng/mL)		CRP/(mg/L)
组别	例数	治疗前	治疗1周后	治疗前	治疗1周后
观察组	25	6.51±1.48	2.73±1.23^a	68.02±10.16	23.92±5.97^a
对照组	25	6.72±1.71	5.16±1.58^a	67.68±9.98	45.93±9.29^a
t值		1.021	4.833	1.572	7.081
P值		0.282	0.034	0.724	< 0.001
注: 与同组治疗前比较，^aP＜0.05。

下载: 导出CSV

表 4 2组脓毒症患者治疗前后TLR9和NF-κB比较(x±s)

组别	例数	TLR9/(ng/mL)		NF-κB/(pg/mL)
组别	例数	治疗前	治疗1周后	治疗前	治疗1周后
观察组	25	15.08±1.74	8.62±0.76^a	100.36±10.89	58.63±5.97^a
对照组	25	15.21±1.81	14.96±1.39	100.23±10.57	99.98±9.68
t值		1.963	5.871	2.352	8.361
P值		0.334	0.031	0.642	0.001
注：与同组治疗前比较，^aP＜0.05。

下载: 导出CSV

表 5 2组脓毒症患者治疗前后SOFA和APACHE Ⅱ评分比较(x±s)

组别	例数	SOFA评分		APACHEⅡ评分
组别	例数	治疗前	治疗1周后	治疗前	治疗1周后
观察组	25	10.06±2.04	4.62±0.55^a	21.37±8.78	15.97±7.67^a
对照组	25	10.21±2.81	8.17±2.39^a	21.18±9.85	18.74±7.18^a
t值		1.042	3.672	2.012	5.354
P值		0.733	0.001	0.923	0.002
注：与同组治疗前比较，^aP＜0.05。

下载: 导出CSV

参考文献(28)

[1]	江伟, 杜斌. 中国脓毒症流行病学现状[J]. 医学研究生学报, 2019, 32(1): 5-8. https://www.cnki.com.cn/Article/CJFDTOTAL-JLYB201901002.htm
[2]	李宁, 夏胜兵. 分析脓毒症患者细胞免疫、体液免疫指标与病情严重程度及预后的关系[J]. 临床研究, 2020, 28(4): 27-28. doi: 10.3969/j.issn.1674-7860.2020.04.008
[3]	曹钰, 柴艳芬, 邓颖, 等. 中国脓毒症/脓毒性休克急诊治疗指南(2018)[J]. 临床急诊杂志, 2018, 19(9): 567-588. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZLC201809001.htm
[4]	KEELEY A, HINE P, NSUTEBU E. The recognition and management of sepsis and septic shock: A guide for non-intensivists[J]. Postgrad Med J, 2017, 93(1104): 626-634. doi: 10.1136/postgradmedj-2016-134519
[5]	FLEISCHMANN C, SCHERAG A, ADHIKARI NK, et al. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations[J]. Am J Respir Crit Care Med, 2016, 193(3): 259-72. doi: 10.1164/rccm.201504-0781OC
[6]	HUANG M, CAI S, SU J. The Pathogenesis of sepsis and potential therapeutic targets[J]. Int J Mol Sci, 2019, 20(21): 5376. doi: 10.3390/ijms20215376
[7]	VALLEY T S, NALLAMOTHU B K, HEUNG M, et al. Hospital variation in renal replacement therapy for sepsis in the united states[J]. Crit Care Med, 2018, 46(2): e158-e165. doi: 10.1097/CCM.0000000000002878
[8]	戴琳琳, 崔颖. 低分子肝素抗凝治疗对ICU脓毒症患者凝血功能和炎症反应的影响[J]. 河北医科大学学报, 2018, 39(1): 100-104. doi: 10.3969/j.issn.1007-3205.2018.01.022
[9]	郭伟, 李平, 陈翠, 等. 脓毒症诱导T细胞功能紊乱及免疫治疗进展[J]. 临床急诊杂志, 2020, 21(9): 758-762. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZLC202009017.htm
[10]	WAND S, KLAGES M, KIRBACH C, et al. IgM-Enriched immunoglobulin attenuates systemic endotoxin activity in early severe sepsis: A before-after cohort study[J]. PLoS One, 2016, 11(8): e0160907. doi: 10.1371/journal.pone.0160907
[11]	符瑜, 吴少敏, 曾昭凡. 乌司他丁联合胸腺肽对重症肺炎患者呼吸功能和炎症应激反应的影响[J]. 中国医药, 2019, 14(8): 1159-1163. doi: 10.3760/j.issn.1673-4777.2019.08.010
[12]	黎汝婷, 刘华锋, 姚翠微. 胸腺肽α1在肾病综合征中的应用及研究进展[J]. 海南医学, 2020, 31(22): 2975-2978. doi: 10.3969/j.issn.1003-6350.2020.22.030
[13]	赵丽红. 小青龙汤联合阿奇霉素治疗小儿肺炎疗效观察及对T淋巴细胞亚群细胞因子的影响[J]. 新中医, 2020, 52(16): 30-33. https://www.cnki.com.cn/Article/CJFDTOTAL-REND202016009.htm
[14]	韩林, 熊滨. 乌司他丁联合胸腺肽对脓毒血症患者血清炎症因子、黏附因子及免疫细胞亚群的影响[J]. 山东医药, 2017, 57(41): 91-93. doi: 10.3969/j.issn.1002-266X.2017.41.031
[15]	文艳琼, 朱柏珍, 黄爱群, 等. 血清PCT和CRP联合检测对脓毒症患者的诊断价值[J]. 实验与检验医学, 2016, 34(2): 231-233. doi: 10.3969/j.issn.1674-1129.2016.02.037
[16]	陈静波. C-反应蛋白、降钙素原对脓毒症患者早期诊断及病情评估的应用价值[J]. 国际检验医学杂志, 2020, 41(2): 242-244. doi: 10.3969/j.issn.1673-4130.2020.02.029
[17]	赵涛, 李三喜, 谢昌鸿. 胸腺肽α1对ICU脓毒症患者免疫功能及血清降钙素原的影响[J]. 世界临床药物, 2019, 40(10): 723-727. https://www.cnki.com.cn/Article/CJFDTOTAL-GWHH201910011.htm
[18]	黄赛. 胸腺肽联合头孢哌酮钠舒巴坦对呼吸机相关性肺炎患者C反应蛋白及呼吸功能的影响[J]. 航空航天医学杂志, 2019, 30(11): 1391-1393. doi: 10.3969/j.issn.2095-1434.2019.11.049
[19]	HOU Y, LU X, ZHANG Y. IRAK inhibitor protects the intestinal tract of necrotizing enterocolitis by inhibiting the Toll-Like receptor(TLR) Infla-mmatory signaling pathway in rats[J]. Med Sci Monit, 2018, 24(5): 3366-3373. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992962/
[20]	LI Z, ZHANG X, ZHOU H, et al. Exogenous S-nitrosoglutathione attenuates inflammatory response and intestinal epithelial barrier injury in endotoxemic rats[J]. J Trauma Acute Care Surg, 2016, 80(6): 977-984. doi: 10.1097/TA.0000000000001008
[21]	HUANG C, PAN L, LIN F, et al. Monoclonal antibody against Toll-like receptor 4 attenuates ventilator-induced lung injury in rats by inhibiting MyD88 and NF-κB dependent signaling[J]. Int J Mol Med, 2017, 39(3): 693-700. doi: 10.3892/ijmm.2017.2873
[22]	YAN Y, LU B, LI P, et al. NOD receptor and TLR9 modulation in severe acute pancreatitis-Induced intestinal injury[J]. Mol Med Rep, 2017, 16(6): 8471-8480. doi: 10.3892/mmr.2017.7661
[23]	董丽敏, 周南, 孙莹杰. 右美托咪定改善感染性休克大鼠急性肺损伤及对TLR9/NF-κB通路表达的影响[J]. 解剖科学进展, 2019, 25(6): 626-629, 633. https://www.cnki.com.cn/Article/CJFDTOTAL-JPKX201906004.htm
[24]	NAIR R, BHANDARY N M, D'SOUZA A D. Initial sequential organ failure assessment score versus simplified acute physiology score to analyze multiple organ dysfunction in infectious diseases in intensive care unit[J]. Indian J Crit Care Med, 2016, 20(4): 210-215. doi: 10.4103/0972-5229.180041
[25]	明颖, 闫妹姝, 刘秋霞, 等. 脓毒症患者血清降钙素原、炎症因子水平与APACHEⅡ、SOFA评分的相关性[J]. 现代医学, 2020, 48(3): 357-361. https://www.cnki.com.cn/Article/CJFDTOTAL-TDYX202003016.htm
[26]	肖百芳, 张亚娟, 王笑云, 等. APACHEⅡ评分联合乳酸评估脓毒症在ICU出科时间的应用价值[J]. 齐齐哈尔医学院学报, 2020, 41(10): 1232-1234. doi: 10.3969/j.issn.1002-1256.2020.10.017
[27]	明颖, 闫妹姝, 刘秋霞, 等. 脓毒症患者血清降钙素原、炎症因子水平与APACHEⅡ、SOFA评分的相关性[J]. 现代医学, 2020, 48(3): 357-361. https://www.cnki.com.cn/Article/CJFDTOTAL-TDYX202003016.htm
[28]	卢铭, 李佳峻. 乌司他丁联合胸腺肽α1对脓毒症患者外周血T淋巴细胞亚群及炎症因子水平影响[J]. 创伤与急危重病医学, 2018, 6(6): 369-371, 374.