The purpose of this study was to explore the effects of emodin on renal injury in a BXSB mouse model of lupus and its mechanisms. BXSB mice were fed different concentrations of emodin (0, 5, 10 and 20 mg/kg.d), and the levels of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-alpha (TNF-α) and fibronectin (FN) levels in the glomeruli and serum levels of the anti-dsDNA antibody were determined. Mesangial cells (MCs) were cultured in vitro, and IgG-type anti-dsDNA antibody and/or emodin were added to the MC culture supernatant. In addition, a TNF-α siRNA was transfected into MCs to explore the mechanism of action of emodin. The results showed that the mice fed emodin presented decreases in the urinary protein content and glomerular TNF-α, ICAM-1 and FN levels (P<0.05). Moreover, the urine protein, TNF-α, ICAM-1 and FN levels were decreased in a dose-dependent manner (P<0.05). In vitro, the anti-dsDNA antibody group exhibited increased levels of ICAM-1 and TNF-α (P<0.05), and the anti-dsDNA antibody group showed myofibroblast-like structural changes. The aforementioned indexes were decreased in the emodin group (P<0.05), and the extent of transdifferentiation was significantly reduced. Moreover, the level of ICAM-1 decreased with the downregulation of TNF-α (P<0.05). Emodin reduced the urine protein levels and serum levels of the anti-dsDNA antibody in a mouse model of lupus nephritis (LN). The underlying mechanism may be related to decreased levels of TNF-α, ICAM-1 and FN and the inhibition of dsDNA antibody-induced MC damage.

中文翻译：

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大黄素通过调节TNF-α/ ICAM-1改善BXSB小鼠的肾损伤。

这项研究的目的是探讨大黄素对狼疮BXSB小鼠模型肾脏损害的作用及其机制。给BXSB小鼠饲喂不同浓度的大黄素（0、5、10和20 mg / kg.d）以及细胞间粘附分子1（ICAM-1），肿瘤坏死因子α（TNF-α）和纤连蛋白的水平测定了抗dsDNA抗体的肾小球中的（FN）水平和血清水平。肾小球系膜细胞（MCs）在体外培养，并将IgG型抗dsDNA抗体和/或大黄素添加到MC培养上清液中。此外，将TNF-αsiRNA转染到MC中以探索大黄素的作用机理。结果表明，饲喂大黄素的小鼠尿蛋白含量降低，肾小球TNF-α，ICAM-1和FN水平降低（P <0.05）。此外，尿蛋白TNF-α ICAM-1和FN水平以剂量依赖性方式降低（P <0.05）。在体外，抗dsDNA抗体组的ICAM-1和TNF-α水平升高（P <0.05），而抗dsDNA抗体组的肌成纤维细胞样结构改变。大黄素组的上述指标降低（P <0.05），转分化程度明显降低。此外，ICAM-1的水平随着TNF-α的下调而降低（P <0.05）。大黄素降低了狼疮性肾炎（LN）小鼠模型的尿蛋白水平和抗dsDNA抗体的血清水平。潜在的机制可能与TNF-α，ICAM-1和FN的水平降低以及dsDNA抗体诱导的MC损伤的抑制有关。抗dsDNA抗体组的ICAM-1和TNF-α水平升高（P <0.05），抗dsDNA抗体组的肌成纤维细胞样结构改变。大黄素组的上述指标降低（P <0.05），转分化程度明显降低。此外，ICAM-1的水平随着TNF-α的下调而降低（P <0.05）。大黄素降低了狼疮性肾炎（LN）小鼠模型的尿蛋白水平和抗dsDNA抗体的血清水平。潜在的机制可能与TNF-α，ICAM-1和FN的水平降低以及dsDNA抗体诱导的MC损伤的抑制有关。抗dsDNA抗体组的ICAM-1和TNF-α水平升高（P <0.05），抗dsDNA抗体组的肌成纤维细胞样结构改变。大黄素组的上述指标降低（P <0.05），转分化程度明显降低。此外，ICAM-1的水平随着TNF-α的下调而降低（P <0.05）。大黄素降低了狼疮性肾炎（LN）小鼠模型的尿蛋白水平和抗dsDNA抗体的血清水平。潜在的机制可能与TNF-α，ICAM-1和FN的水平降低以及dsDNA抗体诱导的MC损伤的抑制有关。转分化程度明显降低。此外，ICAM-1的水平随着TNF-α的下调而降低（P <0.05）。大黄素降低了狼疮性肾炎（LN）小鼠模型的尿蛋白水平和抗dsDNA抗体的血清水平。潜在的机制可能与TNF-α，ICAM-1和FN的水平降低以及dsDNA抗体诱导的MC损伤的抑制有关。转分化程度明显降低。此外，ICAM-1的水平随着TNF-α的下调而降低（P <0.05）。大黄素降低了狼疮性肾炎（LN）小鼠模型的尿蛋白水平和抗dsDNA抗体的血清水平。潜在的机制可能与TNF-α，ICAM-1和FN的水平降低以及dsDNA抗体诱导的MC损伤的抑制有关。