School of Life Science and Technology, Wuhan Polytechnic University, Wuhan, China.
School of Animal Science and Nutrition Engineering, Wuhan Polytechnic University, Wuhan, China.
Nephrology (Carlton). 2023 Jun;28(6):315-327. doi: 10.1111/nep.14159. Epub 2023 Apr 24.
Inflammation and apoptosis are main pathological processes that lead to the development of hyperuricemic nephropathy (HN). This study aims to explore whether baicalin (BA) and baicalein (BAI) can relieve the damage through PI3K/AKT/NF-κB signal pathway and provide more reliable and precise evidence for the treatment of HN.
HN mice were induced by yeast extract with potassium oxonate (PO), and HK-2 cells were induced by monosodium urate (MSU). Molecular docking, western blot, q-PCR, and other methods were used to explore the changes of various indicators in HN mice and HK-2 cells.
Molecular docking results showed that BA and BAI had good binding ability with PI3K, AKT, p65 and IκBα. BA and BAI significantly ameliorated the levels of renal function, decreased the p-PI3K, p-AKT and p-p65 expression, down-regulated the BAX/BCL2 and CASP3, and blunted the mRNA levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-18 in both renal tissue of HN mice and HK-2 cells induced by MSU. BA and BAI also decreased the oxidative stress level of MSU-induced HK-2 cells.
BA and BAI were confirmed to attenuate HN through alleviating renal inflammatory and apoptosis in cells and tissues by inhibiting PI3K/AKT/NF-κB pathway. BA and BAI were expected to be developed as new anti-HN drugs.
炎症和细胞凋亡是导致高尿酸血症肾病（HN）发展的主要病理过程。本研究旨在探讨黄芩苷（BA）和黄芩素（BAI）是否可以通过 PI3K/AKT/NF-κB 信号通路缓解这种损伤，并为 HN 的治疗提供更可靠、更精确的证据。
采用酵母抽提物加氧嗪酸钾（PO）诱导 HN 小鼠模型，采用尿酸单钠（MSU）诱导 HK-2 细胞模型。采用分子对接、western blot、q-PCR 等方法，探讨 HN 小鼠和 MSU 诱导的 HK-2 细胞中各指标的变化。
分子对接结果表明，BA 和 BAI 与 PI3K、AKT、p65 和 IκBα均具有良好的结合能力。BA 和 BAI 显著改善了肾功能水平，降低了 p-PI3K、p-AKT 和 p-p65 的表达，下调了 BAX/BCL2 和 CASP3，并减弱了 HN 小鼠肾组织和 MSU 诱导的 HK-2 细胞中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和 IL-18 的 mRNA 水平。BA 和 BAI 还降低了 MSU 诱导的 HK-2 细胞的氧化应激水平。
BA 和 BAI 通过抑制 PI3K/AKT/NF-κB 通路，减轻细胞和组织中的肾炎症和细胞凋亡，从而减轻 HN。BA 和 BAI 有望被开发为新型抗 HN 药物。
