张雁宇, 吕欣, 黄晓光, 任小军, 王雪, 于为民. 双硫仑作用机制及其在治疗抗肾小球基底膜型肾小球肾炎中的研究进展[J]. 临床肾脏病杂志, 2024, 24(3): 249-253. DOI: 10.3969/j.issn.1671-2390.2024.03.011
    引用本文: 张雁宇, 吕欣, 黄晓光, 任小军, 王雪, 于为民. 双硫仑作用机制及其在治疗抗肾小球基底膜型肾小球肾炎中的研究进展[J]. 临床肾脏病杂志, 2024, 24(3): 249-253. DOI: 10.3969/j.issn.1671-2390.2024.03.011
    Zhang Yan-yu, Lyu Xin, Huang Xiao-guang, Ren Xiao-jun, Wang Xue, Yu Wei-min. Mechanism of action of disulfiram and research advances in anti-glomerular basement membrane type glomerulonephritis[J]. Journal of Clinical Nephrology, 2024, 24(3): 249-253. DOI: 10.3969/j.issn.1671-2390.2024.03.011
    Citation: Zhang Yan-yu, Lyu Xin, Huang Xiao-guang, Ren Xiao-jun, Wang Xue, Yu Wei-min. Mechanism of action of disulfiram and research advances in anti-glomerular basement membrane type glomerulonephritis[J]. Journal of Clinical Nephrology, 2024, 24(3): 249-253. DOI: 10.3969/j.issn.1671-2390.2024.03.011

    双硫仑作用机制及其在治疗抗肾小球基底膜型肾小球肾炎中的研究进展

    Mechanism of action of disulfiram and research advances in anti-glomerular basement membrane type glomerulonephritis

    • 摘要: 双硫仑作为一种治疗慢性酒精中毒的药物在临床中广泛使用。近年来,研究者提出了双硫仑治疗癌症的具体机制,如抑制乙醛脱氢酶(acetaldehyde dehydrogenase,ALDH)的活性、提高细胞内活性氧(reactive oxygen species,ROS)的浓度、抑制核因子 kappa-B(nuclear factor kappa-B,NF-κB)的活性,促进与核蛋白定位蛋白4(nuclear protein localization protein 4,NPL4)的结合、抑制FROUNT蛋白等,并在多种癌症模型中证明了双硫仑的抗癌活性。抗肾小球基底膜型肾小球肾炎是急进性肾小球肾炎中的一种类型,该病一旦被确诊,就需要第一时间给予治疗,尽量帮助患者缓解症状、改善预后。研究表明,双硫仑可通过抑制C-C趋化因子受体2型/C-C趋化因子受体5型(C-C chemokine receptor type 2/C-C chemokine receptor type 5,CCR-2/CCR-5)和FROUNT蛋白之间的相互作用来抑制巨噬细胞的迁移、聚集、活化来缓解抗肾小球基底膜型肾小球肾炎,这表明双硫仑对该类患者具有潜在的治疗价值。本文简要回顾了双硫仑最新研究中阐明的相关作用分子机制,展望了未来双硫仑作为新的药物治疗抗肾小球基底膜型肾小球肾炎的前景。

       

      Abstract: Disulfiram is widely applied for treating chronic alcoholism. In recent years, researchers have proposed specific anti-cancer mechanisms by disulfiram, such as arresting the activity of acetaldehyde dehydrogenase (ALDH) and boosting intracellular reactive oxygen species (ROS)(reactive oxygen species). A higher concentration of ROS suppressed the activity of nuclear factor kappa-B (NF-κB) and promoted the conjugation between ROS and nuclear protein localization protein 4 (nuclear protein localization protein 4). Conjugation of NPL4, an inhibition of FROUNT protein and anti-cancer activity of disulfiram have been demonstrated in various cancer models. Anti-glomerular basement membrane glomerulonephritis is one type of acute glomerulonephritis. Upon a definite diagnosis, it should be promptly treated for relieving symptoms and improving outcomes. Disulfiram could antagonize C-C chemokine receptor type 2 and C-C chemokine receptor type 5 through suppressing C-C chemokine receptor type 2/C-C chemokine receptor type 5, CCR-2/CCR-5) and FROUNT protein interacted to suppress the migration, aggregation and activation of macrophages for alleviating anti-glomerular basement membrane type glomerulonephritis. It indicated that disulfiram had some potential therapeutic value. This review focused upon the molecular mechanism of disulfiram. And disulfiram may become a new agent for anti-glomerular basement membrane glomerulonephritis.

       

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