■本研究旨在探讨大黄酚对肾脏纤维化的抑制作用及其分子机制。
■最初,通过网络药理学分析预测大黄酚的潜在靶标,并使用维恩图和STRING数据库构建了这些靶标的蛋白质-蛋白质相互作用网络。GO富集分析预测了大黄酚治疗肾纤维化的生物学过程。随后,使用单侧输尿管梗阻(UUO)诱导的CKD小鼠模型和HK-2细胞模型进行体内和体外实验,分别。在老鼠模型中,不同剂量的大黄酚通过生化指标评估其肾脏保护作用,组织学检查,和免疫荧光染色。在细胞模型中,使用蛋白质印迹和流式细胞术评估了大黄酚对Trx-1/JNK/Cx43通路的调节作用.
■大黄酚治疗可显着改善UUO小鼠模型的肾功能障碍和组织病理学损害,伴随着血清氧化应激标志物的减少。此外,大黄酚显著上调肾组织中Trx-1的表达,抑制JNK/Cx43信号通路的激活。在细胞层面,大黄酚增强Trx-1的活性并下调JNK/Cx43信号通路,从而抑制TGF-β诱导的氧化应激和细胞凋亡。
■这项研究证明了大黄酚对肾脏纤维化的显着抑制作用,通过激活Trx-1来抑制JNK/Cx43通路。这些发现为大黄酚作为肾脏纤维化治疗剂的潜在用途提供了实验支持。
UNASSIGNED: This study aimed to investigate the inhibitory effect of chrysophanol on renal fibrosis and its molecular mechanism.
UNASSIGNED: Initially, potential targets of chrysophanol were predicted through network pharmacology analysis, and a protein-protein interaction network of these targets was constructed using Venn diagrams and the STRING database. GO enrichment analysis predicted the biological process of chrysophanol in treating renal fibrosis. Subsequently, both in vivo and in vitro experiments were conducted using unilateral ureteral obstruction (UUO) induced CKD mouse model and HK-2 cell model, respectively. In the mouse model, different doses of chrysophanol were administered to assess its renal protective effects through biochemical indicators, histological examination, and immunofluorescence staining. In the cell model, the regulatory effect of chrysophanol on the Trx-1/
JNK/Cx43 pathway was evaluated using western blotting and flow cytometry.
UNASSIGNED: Chrysophanol treatment significantly ameliorated renal dysfunction and histopathological damage in the UUO mouse model, accompanied by a reduction in serum oxidative stress markers. Furthermore, chrysophanol markedly upregulated the expression of Trx-1 in renal tissues and inhibited the activation of the
JNK/Cx43 signaling pathway. At the cellular level, chrysophanol enhanced the activity of Trx-1 and downregulated the
JNK/Cx43 signaling pathway, thereby inhibiting TGF-β induced oxidative stress and cell apoptosis.
UNASSIGNED: This study demonstrated a significant inhibitory effect of chrysophanol on renal fibrosis, mediated by the activation of Trx-1 to inhibit the
JNK/Cx43 pathway. These findings provide experimental support for the potential use of chrysophanol as a therapeutic agent for renal fibrosis.