背景:青蒿-别甲中药对(QB)是“解毒祛瘀滋阴方”的核心中药对,是临床治疗系统性红斑狼疮(SLE)的常用中药对之一。先前的研究表明,QB降低了MRL/lpr小鼠血清和肾脏中炎性细胞因子如IL-6和TNF-α的表达。此外,它抑制肾脏和主动脉中TLR4和MyD88的表达,并减少治疗后肾脏补体C3和主动脉斑块的沉积。这些发现表明QB对狼疮大鼠具有预防和治疗作用。
目的:本研究旨在探讨青蒿-别甲药对抗SLE与动脉粥样硬化活性的潜在机制。
方法:使用HERB数据库确定QB的药物靶标,而与SLE和动脉粥样硬化相关的目标是从GeneCards数据库中检索的。然后使用具有GO和KEGG途径富集分析的蛋白质-蛋白质相互作用(PPI)网络来分析这些药物和疾病靶标的交集。在体内,通过腹膜内注射前列腺素并继续喂食高脂饮食,诱导载脂蛋白E缺陷型(ApoE-/-)小鼠发展为SLE-AS。观察羟氯喹灌胃治疗12周后相关指标的变化,QB,Q(单独清豪),和B(单独别家)。来自ApoE-/-小鼠的骨髓来源的巨噬细胞和Raw264.7巨噬细胞用于探索QB治疗的机制。
结果:各治疗组小鼠血清炎性细胞因子水平及肝脏病理改变均有不同程度的改善。此外,主动脉粥样斑块形成减少,血脂异常改善.此外,QB抑制ABCA1/G1的表达,提示其在调节巨噬细胞极化中的作用。
结论:QB显示治疗SLE-AS的明确疗效,其治疗机制可能涉及通过促进胆固醇流出调节巨噬细胞表型。
BACKGROUND: Qinghao-Biejia herb pair (QB) is the core herb pair of \"Jieduquyuziyin prescription\" and is one of the commonly used herb pairs for the clinical treatment of systemic lupus erythematosus (SLE). Previous studies have shown that QB reduces the expression of inflammatory cytokines like IL-6 and TNF-α in the serum and kidney of MRL/lpr mice. Additionally, it inhibits the expression of TLR4 and MyD88 in the kidney and aorta and reduces the deposition of renal complement C3 and aortic plaque after treatment. These findings suggest that QB has a preventive and therapeutic effect on lupus rats.
OBJECTIVE: This study sought to investigate the mechanisms underlying the anti-SLE combined with atherosclerosis activity of the Qinghao-Biejia herb pair.
METHODS: Drug targets for QB were identified using the HERB database, while targets associated with SLE and atherosclerosis were retrieved from the GeneCards database. The intersection of these drug and disease targets was then analyzed using a protein-protein interaction (PPI) network with GO and KEGG pathway enrichment analysis. In vivo, apolipoprotein E-deficient (ApoE-/-) mice were induced to develop SLE-AS by intraperitoneal injection of pristane and continued feeding of a high-fat diet. The changes in relevant indexes were observed after 12 weeks of gavage treatment with hydroxychloroquine, QB, Q (Qinghao alone), and B (Biejia alone). Bone marrow-derived macrophages from ApoE-/- mice and Raw 264.7 macrophages were used to explore the mechanisms of QB treatment.
RESULTS: The levels of inflammatory cytokines in serum and pathological liver changes in mice were improved to varying degrees in the treatment groups. Additionally, there was a reduction in aortic atheromatous plaque formation and some improvement in cholesterol efflux. Furthermore, QB suppressed the expression of inflammatory cytokines in M1 macrophages, suggesting a role in regulating macrophage polarization.
CONCLUSIONS: QB demonstrates clear efficacy for treating SLE-AS, and its therapeutic mechanism may involve the regulation of macrophage phenotypes by promoting cholesterol efflux.