慢加急性乙型肝炎肝衰竭患者外周血巨噬细胞极化和TXNIP/NLRP3水平与预后的关系探讨*

doi:10.3969/j.issn.1672-5069.2023.01.017

实用肝脏病杂志 ›› 2023, Vol. 26 ›› Issue (1): 63-66.doi: 10.3969/j.issn.1672-5069.2023.01.017

慢加急性乙型肝炎肝衰竭患者外周血巨噬细胞极化和TXNIP/NLRP3水平与预后的关系探讨^*

邵思萌, 高峰, 蒋磊, 魏亚虎, 赵威

110141 沈阳市武警辽宁省总队医院质量管理科(邵思萌,高峰,魏亚虎,赵威);锦州医科大学附属第一医院消化内科(蒋磊)

收稿日期:2022-04-25 出版日期:2023-01-10 发布日期:2023-02-07
通讯作者: 赵威,E-mail:zw1993090157@163.com
作者简介:邵思萌,女,35岁,大学本科,主治医师。E-mail:meng_lovely1987@126.com
基金资助:
^*辽宁省教育厅科学研究基金资助项目(编号:3206-740)

Polarization of peripheral blood macrophages and PBMCs TXNIP/NLRP3 mRNA changes in patients with hepatitis B virus acute-on-chronic liver failure

Shao Simeng, Gao Feng, Jiang Lei, et al

Department of Medical Quality Management, General Hospital, Armed Police Corps, Shenyang 110141, Liaoning Province, China

Received:2022-04-25 Online:2023-01-10 Published:2023-02-07

摘要/Abstract

摘要： 目的探讨慢加急性乙型肝炎肝衰竭(HBV-ACLF)患者外周血巨噬细胞极化和外周血单个核细胞(PBMCs)硫氧还蛋白相互作用蛋白(TXNIP)/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)水平变化。方法 2019年6年～2020年6月我院收治的HBV-ACLF患者57例和慢性乙型肝炎(CHB)患者43例,使用流式细胞仪检测外周血M1/M2型巨噬细胞比率,分离PBMCs,采用实时荧光定量RT-PCR法检测TXNIP、NLRP3和半胱氨酸蛋白酶-1(caspase-1)mRNA水平,采用ELISA法检测血清白介素-6(IL)-6、IL-10和肿瘤坏死因子-α(TNF-α)。结果 HBV-ACLF组M1型巨噬细胞比率和M1/M2细胞比值分别为(3.5±0.4)%和(1.2±0.2),显著高于CHB组【分别为(2.1±0.2)%和(0.6±0.1),P<0.05】,而M2型巨噬细胞比率为(2.5±0.3)%,显著低于CHB组【(4.1±0.4)%,P<0.05】;HBV-ACLF组血清IL-6和TNF-α水平分别为(37.9±4.2)ng/L和(2.3±0.2)pg/mL,显著高于CHB组【分别为(28.8±3.6)ng/L和(1.2±0.1)pg/mL,P<0.05】,而血清IL-10水平为(1.4±0.2)pg/mL,显著低于CHB组【(2.9±0.3)pg/mL,P<0.05】;HBV-ACLF组PBMCs NLRP3、TXNIP和caspase-1 mRNA水平分别为(0.5±0.1)、(0.7±0.1)和(1.2±0.1),显著低于CHB组【分别为(0.8±0.2)、(1.0±0.1)和(1.6±0.2),P<0.05】;15例死亡患者外周血M1型巨噬细胞比率为(4.1±0.4)%,显著高于42例生存组【(3.3±0.3)%,P<0.05】,而M2型巨噬细胞比率、PBMCs NLRP3和TXNIP mRNA水平分别为(1.9±0.2)%、(0.2±0.1)和(0.4±0.1),显著低于生存组【分别为(2.7±0.3)%、(0.6±0.1)和(0.8±0.1),P<0.05】。结论 HBV-ACLF患者外周血巨噬细胞向促炎方向极化,而TXNIP和NLRP3 mRNA水平下调可能与免疫功能被抑制有关。

关键词: 慢加急性肝衰竭, 巨噬细胞, 硫氧还蛋白相互作用蛋白, 核苷酸结合寡聚化结构域样受体蛋白3, 预后

Abstract: Objective The aim of this study was to explore the polarization of peripheral blood macrophages and peripheral blood mononuclear lymphocyte (PBMC) thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligo-merization domain-like receptor protein 3 (NLRP3) mRNA changes in patients with hepatitis B virus acute-on-chronic liver failure (HBV-ACLF). Methods 57 patients with HBV-ACLF and 43 patients with chronic hepatitis B (CHB) were enrolled in our hospital between June 2019 and June 2020, and the percentages of peripheral blood M1 and M2 macrophages were detected by flow cytometry. The PBMC TXNIP, NLRP3 and cysteine protease-1 (caspase-1) mRNA were assayed by real-time fluorescence quantification RT-PCR. Serum interleukin-6 (IL)-6, IL-10 and tumor necrosis factor-α (TNF-α) were detected by ELISA. Results The percentage of M1 macrophages and M1/M2 cell ratio in patients with HBV-ACLF were (3.5±0.4)% and (1.2±0.2), significantly higher than [(2.1±0.2)% and (0.6±0.1), P<0.05], while the percentage of M2 macrophages was (2.5±0.3)%, significantly lower than [(4.1±0.4)%, P<0.05] in patients with CHB; serum IL-6 and TNF-α in patients with HBV-ACLF were (37.9±4.2) ng/L and (2.3±0.2) pg/mL, significantly higher than [(28.8±3.6) ng/L and (1.2±0.1) pg/mL, respectivley, P<0.05], while serum IL-10 level was (1.4±0.2) pg/mL, significantly lower than [(2.9±0.3) pg/mL, P<0.05] in patients with CHB; the PBMCs NLRP3, TXNIP and caspase-1 mRNA in patients with HBV-ACLF were (0.5±0.1), (0.7±0.1) and (1.2±0.1), all significantly lower than [(0.8±0.2), (1.0±0.1) and (1.6±0.2), respectively, P<0.05] in patients with CHB; the percentage of PBMC M1 macrophages in 15 dead patients was (4.1±0.4) %, significantly higher than [(3.3±0.3)%, P<0.05], while the percentage of M2 macrophages, PBMCs NLRP3 and TXNIP mRNA were (1.9±0.2)%, (0.2±0.1) and (0.4±0.1), significantly lower than [(2.7±0.3)%,(0.6±0.1) and (0.8±0.1), respectively, P<0.05] in 42 survivals. Conclusion The peripheral blood macrophages are polarized in the pro-inflammatory direction and the down-regulation of TXNIP and NLRP3 mRNA might be related to immunosuppression in patients with HBV-ACLF.

Key words: Acute-on-chronic liver failure, Macrophage polarization, Thioredoxin-interacting protein, Nucleotide-binding oligo-merization domain-like receptor protein 3, Prognosis

邵思萌, 高峰, 蒋磊, 魏亚虎, 赵威. 慢加急性乙型肝炎肝衰竭患者外周血巨噬细胞极化和TXNIP/NLRP3水平与预后的关系探讨^*[J]. 实用肝脏病杂志, 2023, 26(1): 63-66.

Shao Simeng, Gao Feng, Jiang Lei, et al. Polarization of peripheral blood macrophages and PBMCs TXNIP/NLRP3 mRNA changes in patients with hepatitis B virus acute-on-chronic liver failure[J]. Journal of Practical Hepatology, 2023, 26(1): 63-66.

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慢加急性乙型肝炎肝衰竭患者外周血巨噬细胞极化和TXNIP/NLRP3水平与预后的关系探讨^*

Polarization of peripheral blood macrophages and PBMCs TXNIP/NLRP3 mRNA changes in patients with hepatitis B virus acute-on-chronic liver failure

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