系统性红斑狼疮(SLE)是一种复杂的自身免疫性疾病,超过一半的患者发展为狼疮性肾炎(LN),这显著有助于慢性肾病(CKD)和终末期肾病(ESRD)。狼疮性肾炎的治疗一直具有挑战性。他克莫司(TAC),一种有效的免疫抑制剂,近年来已越来越多地用于LN的治疗。本文旨在探讨他克莫司治疗LN的作用机制。首先,简要介绍他克莫司的药理特性,包括其作为钙调磷酸酶(CaN)抑制剂的作用,通过抑制T细胞活化和细胞因子产生发挥免疫抑制作用。随后,我们关注他克莫司在LN治疗中的各种其他免疫调节机制,包括它对T细胞的影响,B细胞,和肾脏中的免疫细胞。特别是,我们强调他克莫司对炎症介质的调节作用及其在调节Th1/Th2和Th17/Treg平衡中的重要性。此外,我们综述了它对肌动蛋白细胞骨架的影响,血管紧张素II(AngII)特异性血管收缩,和P-糖蛋白活性,总结其对非免疫机制的影响。最后,我们总结了他克莫司在临床研究和试验中的疗效和安全性。尽管一些研究显示他克莫司治疗LN的显著疗效,它的安全仍然是一个挑战。我们概述了长期使用他克莫司的潜在不良反应,并提供了在临床实践中有效监测和管理这些不良反应的建议。总的来说,他克莫司,作为一种新型的免疫抑制剂,治疗LN具有广阔的前景。当然,需要进一步研究以更好地了解其治疗机制,并确保其在临床实践中的安全性和有效性.
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder, with more than half of the patients developing lupus nephritis (LN), which significantly contributes to chronic kidney disease (CKD) and end-stage renal disease (ESRD). The treatment of lupus nephritis has always been challenging. Tacrolimus (TAC), an effective immunosuppressant, has been increasingly used in the treatment of LN in recent years. This review aims to explore the mechanisms of action of tacrolimus in treating LN. Firstly, we briefly introduce the pharmacological properties of tacrolimus, including its role as a calcineurin (CaN) inhibitor, exerting immunosuppressive effects by inhibiting T cell activation and cytokine production. Subsequently, we focus on various other immunomodulatory mechanisms of tacrolimus in LN therapy, including its effects on T cells, B cells, and immune cells in kidney. Particularly, we emphasize tacrolimus\' regulatory effect on inflammatory mediators and its importance in modulating the Th1/Th2 and Th17/Treg balance. Additionally, we review its effects on actin cytoskeleton, angiotensin II (Ang II)-specific vascular contraction, and P-glycoprotein activity, summarizing its impacts on non-immune mechanisms. Finally, we summarize the efficacy and safety of tacrolimus in clinical studies and trials. Although some studies have shown significant efficacy of tacrolimus in treating LN, its safety remains a challenge. We outline the potential adverse reactions of long-term tacrolimus use and provide suggestions on effectively monitoring and managing these adverse reactions in clinical practice. In general, tacrolimus, as a novel immunosuppressant, holds promising prospects for treating LN. Of course, further research is needed to better understand its therapeutic mechanisms and ensure its safety and efficacy in clinical practice.