【摘要】 目的:从M1/M2巨噬细胞极化探讨解毒祛瘀滋阴方改善降植烷诱导的系统性红斑狼疮(SLE)小鼠多器官损伤的作用机制。方法:将30只BALB/c小鼠分为对照组(腹腔注射PBS,n=6)和SLE模型组(腹腔注射降植烷,n=24)。造模成功后,随机分为SLE组、解毒祛瘀滋阴方组(36 g/kg)、激素组(强的松,5 mg/kg)及解毒祛瘀滋阴方联合激素组,每组6只。连续干预8周。通过流式细胞术检测脾脏、肾脏、关节M1/M2巨噬细胞比例;生化分析评估肾功能(肌酐、尿素氮);HE染色观察肾脏病理;行为学实验(强迫游泳、悬尾、旷场)评价神经精神症状;结合网络药理学解析潜在作用靶点。结果:与SLE组比较,解毒祛瘀滋阴方组及解毒祛瘀滋阴方联合激素组显著降低脾脏、肾脏、关节M1/M2比例(P<0.01),显著改善肾功能指标(肌酐、尿素氮)(P<0.05,P<0.01)及焦虑/抑郁样行为(静止时间减少、运动距离增加)(P<0.01,P<0.05)。网络药理学筛选出405个共同靶点,其中槲皮素可能通过调控CASP8、MMP9等靶点干预巨噬细胞分化。结论:解毒祛瘀滋阴方通过抑制M1/M2巨噬细胞极化减轻SLE多器官损伤,其机制可能与调控巨噬细胞分化相关通路有关。联合激素治疗也有效改善病情,为临床“增效减毒”策略提供实验依据。更多还原

【Abstract】 Objective: To investigate the mechanism by Jiedu Quyu Ziyin Prescription ameliorates multi-organ damage in pristane-induced systemic lupus erythematosus(SLE) mice by regulating M1/M2 macrophage polarization. Methods: Thirty BALB/c mice were divided into control group(intraperitoneal injection of PBS, n=6) and SLE model group(intraperitoneal injection of pristane, n=24). After successful modeling, it was randomly divided into the SLE group, Jiedu Quyu Ziyin Prescription group(36 g/kg), hormone group(Prednisone, 5 mg/kg), and Jiedu Quyu Ziyin Prescription combination hormone group, 6 mice in each group, with continuous intervention for 8 weeks. The proportions of M1/M2 macrophages in spleen, kidney, and joints were detected by flow cytometry; renal function(creatinine, blood urea nitrogen) was evaluated by biochemical analysis; renal pathology was observed by HE staining; neuropsychiatric symptoms were assessed by behavioral tests(forced swimming, tail suspension, open field); and potential targets were analyzed by network pharmacology. Results: Compared with the SLE group, the Jiedu Quyu Ziyin Prescription group and the Jiedu Quyu Ziyin Prescription combination hormone group significantly reduced the M1/M2 ratio in spleen, kidney and joints(P<0.01), improved renal function indicators(creatinine, blood urea nitrogen)(P<0.05, P<0.01), and alleviated anxiety/depression-like behaviors(reduced immobility time, increased movement distance)(P<0.01, P<0.05). Network pharmacology identified 405 common targets, with quercetin potentially intervening in macrophage differentiation by regulating targets, such as CASP8 and MMP9. Conclusion: Jiedu Quyu Ziyin Prescription alleviates multi-organ damage in SLE by inhibiting M1/M2 macrophage polarization. Its mechanism may be related to the regulation of macrophage differentiation pathways. Combined hormone therapy can effectively improve the condition, providing experimental evidence for the clinical strategy of ‘enhancing efficacy while reducing toxicity’.更多还原