Abstract：Abstract: To investigate the mechanisms of luteolin on improving hyperuricemic nephropathy (HN), 14C uric acid (UA) uptake assay was conducted to test the effect of luteolin on uric acid transporter 1 (URAT1). MTT assay was carried out to evaluate the protective effect of luteolin on renal tubular epithelial cell injury in-duced by high UA levels. Based on the established HN mouse model, the changes of serum biochemical in-dexes in mice, including UA, serum creatinine (CR), urea nitrogen (BUN), malondialdehyde (MDA), supero-xide dismutase (SOD) and glutathione (GSH), were detected before and after luteolin treatment. H&E staining and Masson’s trichrome staining were employed to detect the pathological changes and renal fibrosis in mice. The mRNA expression levels of URAT1, transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA), E-cadherin, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and the protein expression levels of URAT1, Nrf2 and HO-1 were separately detected by qRT-PCR and Western-blot. The results showed that luteolin inhibited URAT1-mediated transport of 14C UA in a dose-dependent manner, with an IC50 value of 23.42 μmol/L. MTT assay showed that luteolin significantly improved the cell damage induced by high UA levels. Compared with the HN group, luteolin reduced the serum UA, CR and BUN levels, down-regulated the mRNA and protein expression levels of renal URAT1, improved renal fibro-sis and affected the mRNA levels of TGF-β, α-SMA and E-cadherin. Besides, oxidative stress in kidney was alleviated by up-regulating Nrf2/HO-1 pathway. In conclusion, luteolin can reduce serum UA by inhi-biting URAT1, and significantly ameliorate renal injury and fibrosis due to Nrf2/HO-1 pathway-dependent antioxidant stress response.
引用本文:
严采馨, 田锦鸿, 李 璐, 庞建新, 吴 婷. 木犀草素通过抑制URAT1与调节Nrf2/HO-1通路改善尿酸诱导的肾脏损伤[J]. 生命科学研究, 2022, 26(2): 103-110. YAN Cai-xin, TIAN Jin-hong, LI Lu, PANG Jian-xin, WU Ting. Luteolin Alleviates Hyperuricemic Nephropathy by Inhibiting URAT1 and Regulating Nrf2/HO-1 Pathway. Life Science Research, 2022, 26(2): 103-110.
