联合沙利度胺治疗SLE中甲泼尼龙具有来氟米特不可替代的效果

Methylprednisolone Offers Unique Therapeutic Value over Leflunomide When Used in SLE Combination Therapy with Thalidomide

摘要: 通过比较沙利度胺分别联合来氟米特和甲泼尼龙对系统性红斑狼疮(SLE)小鼠的治疗效果，探究联合疗法治疗SLE中使用来氟米特替代甲泼尼龙的可能性。将C57BL/6J小鼠随机分为空白组、造模组、沙利度胺联合来氟米特和沙利度胺联合甲泼尼龙治疗组，造模组和治疗组通过涂抹咪喹莫特诱导SLE小鼠模型，模型建立后治疗组灌胃沙利度胺联合来氟米特或沙利度胺联合甲泼尼龙药物。治疗结束后，检测小鼠脾脏重量、血清抗ds-DNA抗体浓度、肾脏病理生理、肾组织IgG和IgM沉积和脾细胞转录组等指标变化。结果显示两种疗法皆能缓解SLE造模引起的脾肿胀和肾损伤、减少小鼠肾组织中IgG和IgM沉积、降低免疫细胞增殖，然而与来氟米特相比，甲泼尼龙联合沙利度胺在缓解肾损伤、减少肾组织IgG和IgM沉积和降低B细胞数量方面更显著，能提高ACOD1表达水平，此外，SLE发病标志物如Rbp4、HPX、Cyp2e1等基因表达明显降低。可见虽然来氟米特联合沙利度胺能有效治疗SLE，但其效果弱于甲泼尼龙，因而无法完全替代甲泼尼龙在SLE的应用。

Abstract: By comparing the therapeutic effects of thalidomide combined with leflunomide versus thalidomide combined with methylprednisolone in systemic lupus erythematosus (SLE) mice, this study aimed to investigate the possibility of replacing methylprednisolone with leflunomide in combination therapy for SLE. C57BL/6J mice were randomly divided into a control group, a model group, a thalidomide plus leflunomide treatment group, and a thalidomide plus methylprednisolone treatment group. The model group and the treatment groups were topically treated with imiquimod to induce the SLE mouse model. After model establishment, the treatment groups were administered thalidomide combined with either leflunomide or methylprednisolone via oral gavage. After treatment, parameters such as spleen weight, serum anti-ds-DNA antibody concentration, renal pathophysiology, renal IgG and IgM deposition, and splenocyte transcriptome changes were measured. The results showed that both combination therapies alleviated splenomegaly and renal injury induced by SLE modeling, reduced IgG and IgM deposition in renal tissues, and decreased immune cell proliferation. However, compared with leflunomide, methylprednisolone combined with thalidomide demonstrated more significant effects in mitigating renal injury, reducing renal IgG and IgM deposition, and decreasing B-cell numbers. It also upregulated ACOD1 expression levels. Additionally, the expression of SLE-related markers such as Rbp4, HPX, and Cyp2e1 was significantly reduced. Although thalidomide combined with leflunomide effectively treated SLE, its efficacy was inferior to that of methylprednisolone combination therapy, indicating that leflunomide cannot completely replace methylprednisolone in SLE treatment.