胸腺肽α1对铜绿假单胞菌诱导的支气管扩张大鼠免疫失衡的干预作用

doi:10.3969/j.issn.1671-7171.2022.04.016

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摘要【目的】探讨胸腺肽α1对铜绿假单胞菌诱导的支气管扩张大鼠免疫失衡的干预作用。【方法】60只健康雄性大鼠分为空白对照组、模型组、低剂量胸腺肽组和高剂量胸腺肽组,每组15只,除空白对照组外的三组大鼠均用气管灌注铜绿假单胞菌液制成支气管扩张模型,低剂量胸腺肽组、高剂量胸腺肽组分别腹腔注射1.25 mg/kg、2.50 mg/kg胸腺肽α1,空白对照组和模型组注射等量生理盐水,连续20 d。末次给药24 h后,检测大鼠呼吸功能指标及血清高迁移率族蛋白B1(HMGB1)、晚期糖基化终产物(RAGE)、干扰素-γ(IFN-γ)水平,流式细胞仪检测T细胞亚群分布情况,Western blot检测支气管组织HMGB1、RAGE蛋白表达。【结果】与空白对照组比较,模型组大鼠潮气量、每分钟通气量、IFN-γ水平、CD3⁺含量、CD4⁺含量、CD4⁺/CD8⁺降低(P<0.05),呼吸频率、HMGB1水平、RAGE水平、HMGB1蛋白表达、TLR9蛋白表达升高(P<0.05),CD8⁺含量无显著变化(P>0.05)。与模型组比较,低剂量胸腺肽组和高剂量胸腺肽组大鼠潮气量、每分钟通气量、IFN-γ水平、CD3⁺含量、CD4⁺含量、CD4⁺/CD8⁺升高(P<0.05),呼吸频率、HMGB1水平、RAGE水平、CD8⁺含量、HMGB1蛋白表达、TLR9蛋白表达降低(P<0.05)。【结论】腹腔注射胸腺肽α1可通过抑制HMGB1/RAGE/ Toll样受体9(TLR9)信号通路,阻止铜绿假单胞菌诱导的支气管扩张大鼠体内细胞因子和炎症介质的瀑布效应,提高大鼠免疫功能。

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	吕建宁
	李琼

关键词 ：支气管扩张症, 铜绿假单胞菌/免疫学, 疾病模型,动物, 免疫测定

Abstract：【Objective】To explore interventional effect of thymosin α1 and participation of high mobility group box B1 (HMGB1)/receptor advanced glycation end products (RAGE)/Toll-like receptor 9 (TLR9) signaling pathway on immune imbalance in rats with pseudomonas aeruginosa-induced bronchiectasis. 【Methods】A total of 60 healthy male rats were divided into the blank control group, model group, low-dose and high-dose thymosin groups, with 15 cases in each group. Except blank control group, all rats in the other groups were given tracheal perfusion of Pseudomonas aeruginosa to induce bronchiectasis models. The low-dose and high-dose thymosin groups were intraperitoneally injected with 1.25 and 2.50 mg/kg thymosin α1, while blank control group and the model group were injected with the same volume of normal saline for 20d. At 24h after the last administration, changes of respiratory function monitoring indexes were detected. The levels of serum HMGB1, RAG and interferon-γ (IFN-γ) were detected by ELASA. The distribution of T cell subsets was detected by flow cytometry. The expressions of HMGB1 and RAGE in bronchial tissues were detected by Western blot. 【Results】Compared with the blank control group, the tidal volume, minute ventilation volume, IFN-γ, CD3⁺, CD4⁺ and CD4⁺/CD8⁺ levels decreased in model group (P<0.05), while respiratory rate, levels of HMGB1 and RAGE, expressions of HMGB1 and TLR9 increased (P<0.05).However, there was no significant change in CD8⁺ percentage (P>0.05). Compared with the model group, tidal volume, minute ventilation volume, IFN-γ, CD3⁺, CD4⁺ and CD4⁺/CD8⁺ levels increased in low-dose and high-dose thymosin group (P<0.05), while respiratory rate, levels of HMGB1 and RAGE and CD8⁺, expressions of HMGB1 and TLR9 decreased (P<0.05). 【Conclusion】Intraperitoneal injection of thymosin α1 can prevent the cascade effect of cytokines and inflammatory mediators in bronchiectasis rats induced by Pseudomonas aeruginosa through inhibiting HMGB1/RAGE/TLR9 signaling pathway, which can improve immune function in rats.

Key words： Bronchiectasis Pseudomonas aeruginosa/IM Disease Models, Animal Immunoassay

收稿日期: 2021-12-14

中图分类号:

R562.22

通讯作者: *E-mail:1751612765@qq.com

引用本文:

吕建宁, 李琼. 胸腺肽α1对铜绿假单胞菌诱导的支气管扩张大鼠免疫失衡的干预作用[J]. 医学临床研究, 2022, 39(4): 535-538.
LYU Jian-ning, LI Qiong. Effect of Thymosin α1 on Immune Imbalance in Rats with Pseudomonas Aeruginosa-induced Bronchiectasis. JOURNAL OF CLINICAL RESEARCH, 2022, 39(4): 535-538.

链接本文:

http://journal07.magtech.org.cn/yxlcyj/CN/10.3969/j.issn.1671-7171.2022.04.016 或 http://journal07.magtech.org.cn/yxlcyj/CN/Y2022/V39/I4/535

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