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丙咪嗪在RAW 264.7细胞和BALB/c小鼠感染544期间诱导的免疫调节和细胞内生长抑制。

Imipramine-induced immunomodulation and intracellular growth inhibition during 544 infection in RAW 264.7 cells and BALB/c mice.

作者信息

Aguilar Ched Nicole Turbela, Huy Tran Xuan Ngoc, Nguyen Trang Thi, Salad Said Abdi, Cho Seong Eun, Hong Il-Hwa, Min Wongi, Lee Hu Jang, Kim Suk

机构信息

Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea.

Institute of Applied Sciences, HUTECH University, Ho Chi Minh City, Vietnam.

出版信息

Front Vet Sci. 2025 Jun 16;12:1598106. doi: 10.3389/fvets.2025.1598106. eCollection 2025.

DOI:10.3389/fvets.2025.1598106
PMID:40589729
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12206653/
Abstract

Brucellosis is a significant zoonotic infection with increasing global prevalence. Traditional treatments rely on antibiotic combinations, but challenges such as drug resistance and relapse necessitate the exploration of alternative therapeutic options. Imipramine hydrochloride (ImiP) has shown potential as an adjunctive treatment for infectious diseases. This study investigates the immunomodulatory effects of ImiP in 544 infections in murine macrophages and BALB/c mice. , RAW 264.7 cells exposed to ImiP exhibited reduced replication, decreased nitrite levels, and enhanced bactericidal effects. , ImiP treatment significantly decreased bacterial loads in the spleen (10 mg/kg, ** < 0.01; 20 mg/kg, * < 0.05) and liver (10 mg/kg, ** < 0.01; 20 mg/kg, *** < 0.001), compared to untreated controls. Histopathological analysis revealed minimal liver microgranuloma formation and periportal inflammation in ImiP-treated mice. Moreover, flow cytometry showed decreased CD4 and CD8 T cell expression, while serum cytokine profiling indicated a Th1-driven immune response, characterized by elevated levels of IL-12 and decreased IL-10. These findings suggest that ImiP possesses both immunomodulatory and antibacterial effects, highlighting its potential as an adjunctive therapy for brucellosis.

摘要

布鲁氏菌病是一种重要的人畜共患感染病,在全球的发病率呈上升趋势。传统治疗依赖抗生素联合使用,但耐药性和复发等问题使得探索替代治疗方案成为必要。盐酸丙咪嗪(ImiP)已显示出作为传染病辅助治疗药物的潜力。本研究调查了ImiP对小鼠巨噬细胞和BALB/c小鼠544感染模型的免疫调节作用。暴露于ImiP的RAW 264.7细胞显示出复制减少、亚硝酸盐水平降低和杀菌作用增强。与未治疗的对照组相比,ImiP治疗显著降低了脾脏(10mg/kg,<0.01;20mg/kg,*<0.05)和肝脏(10mg/kg,<0.01;20mg/kg,***<0.001)中的细菌载量。组织病理学分析显示,ImiP治疗的小鼠肝脏微肉芽肿形成和门静脉周围炎症最少。此外,流式细胞术显示CD4和CD8 T细胞表达降低,而血清细胞因子分析表明存在以IL-12水平升高和IL-10水平降低为特征的Th1驱动的免疫反应。这些发现表明ImiP具有免疫调节和抗菌作用,突出了其作为布鲁氏菌病辅助治疗药物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0008/12206653/ba2b08044810/fvets-12-1598106-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0008/12206653/39b4d62223bb/fvets-12-1598106-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0008/12206653/47cab93c1892/fvets-12-1598106-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0008/12206653/b11e0858dd4f/fvets-12-1598106-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0008/12206653/219826877214/fvets-12-1598106-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0008/12206653/774a940a65bd/fvets-12-1598106-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0008/12206653/ba2b08044810/fvets-12-1598106-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0008/12206653/39b4d62223bb/fvets-12-1598106-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0008/12206653/47cab93c1892/fvets-12-1598106-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0008/12206653/b11e0858dd4f/fvets-12-1598106-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0008/12206653/219826877214/fvets-12-1598106-g004.jpg
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本文引用的文献

1
Imipramine Treatment Alters Sphingomyelin, Cholesterol, and Glycerophospholipid Metabolism in Isolated Macrophage Lysosomes.丙咪嗪治疗改变分离的巨噬细胞溶酶体中的神经鞘磷脂、胆固醇和甘油磷酯代谢。
Biomolecules. 2023 Dec 1;13(12):1732. doi: 10.3390/biom13121732.
2
Long ignored but making a comeback: a worldwide epidemiological evolution of human brucellosis.长期被忽视但正在卷土重来:人类布鲁氏菌病的全球流行病学演变
Emerg Microbes Infect. 2024 Dec;13(1):2290839. doi: 10.1080/22221751.2023.2290839. Epub 2024 Feb 19.
3
Imipramine Administration in -Infected Mice Restores Hippocampal Serotonin Levels, Muscle Strength, and Mood, and Decreases Spleen CFU Count.
给感染小鼠注射丙咪嗪可恢复海马体血清素水平、肌肉力量和情绪,并减少脾脏集落形成单位计数。
Pharmaceuticals (Basel). 2023 Oct 27;16(11):1525. doi: 10.3390/ph16111525.
4
Imipramine Induces Apoptosis and Inhibits the Metastatic Potential of Triple-negative Breast Cancer Cells.丙咪嗪诱导三阴性乳腺癌细胞凋亡并抑制其转移潜能。
Anticancer Res. 2023 Jul;43(7):2985-2994. doi: 10.21873/anticanres.16469.
5
The Modulatory Effect of Sodium Propionate Treatment in the Expression of Inflammatory Cytokines and Intracellular Growth of 544 in Raw 264.7 Cells.丙酸钠处理对 Raw 264.7 细胞中炎症细胞因子表达和细胞内生长的调节作用。
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The antidepressant imipramine inhibits breast cancer growth by targeting estrogen receptor signaling and DNA repair events.抗抑郁药丙咪嗪通过靶向雌激素受体信号和 DNA 修复事件抑制乳腺癌生长。
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