Li Ming-Hui, Guan Jin, Chen Zhe, Mo Ju-Xian, Wu Kai-Reng, Hu Xu-Guang, Lan Tian, Guo Jiao
Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, 510006, China; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou, 510006, China; School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, China.
J Ethnopharmacol. 2022 Nov 15;298:115644. doi: 10.1016/j.jep.2022.115644. Epub 2022 Aug 17.
Excessive serum uric acid (SUA) causes hyperuricemic nephropathy (HN), characterized by inflammatory infiltration and tubulointerstitial fibrosis. Most recently, we demonstrated that Fufang Zhenzhu Tiaozhi (FTZ) capsule attenuated diabetic nephropathy through inhibition of renal inflammation and fibrosis. However, whether FTZ ameliorates HN is still unclear.
To determine the protective roles and mechanism of FTZ in mouse renal injury and fibrosis under hyperuricemic condition.
HN mice, induced by potassium oxonate and hypoxanthine, were administrated with 600 and 1200 mg/kg FTZ (intragastrically) daily for three weeks. SUA levels, renal functions and histological changes were analyzed. Western blotting, quantitative real-time PCR (q-PCR) and RNA sequencing were used to identify the roles and underlying mechanism of FTZ in HN mice.
We demonstrated that FTZ treatment mitigated renal injury in mice, as evidenced by the decrease in SUA, serum creatinine (SCr) and cystatin C (Cys C) levels, as well as improved renal histology. FTZ markedly attenuates inflammasome activation, collagen deposition and the imbalance of uric acid transporters. RNA-sequencing revealed a key mechanism involved in the protective effects on HN mice was related to PI3K/AKT/NF-κB pathway. Western blot also confirmed that FTZ diminished the phosphorylation of AKT and p65 in HN mice.
FTZ prevents renal injury, inflammation and fibrosis in HN mice via promoting uric acid excretion and inhibiting PI3K/AKT/NF-κB signaling pathway.
血清尿酸（SUA）过高会导致高尿酸血症肾病（HN），其特征为炎症浸润和肾小管间质纤维化。最近，我们证明了复方珍珠调脂（FTZ）胶囊通过抑制肾脏炎症和纤维化减轻糖尿病肾病。然而，FTZ是否能改善HN仍不清楚。
确定FTZ在高尿酸血症条件下对小鼠肾损伤和纤维化的保护作用及机制。
用氧嗪酸钾和次黄嘌呤诱导HN小鼠，每天灌胃给予600和1200mg/kg FTZ，持续三周。分析SUA水平、肾功能和组织学变化。采用蛋白质免疫印迹法、定量实时聚合酶链反应（q-PCR）和RNA测序来确定FTZ在HN小鼠中的作用及潜在机制。
我们证明FTZ治疗减轻了小鼠的肾损伤，SUA、血清肌酐（SCr）和胱抑素C（Cys C）水平降低以及肾脏组织学改善证明了这一点。FTZ显著减轻炎性小体激活、胶原蛋白沉积和尿酸转运蛋白失衡。RNA测序显示，对HN小鼠保护作用的关键机制与PI3K/AKT/NF-κB通路有关。蛋白质免疫印迹法也证实FTZ降低了HN小鼠中AKT和p65的磷酸化水平。
FTZ通过促进尿酸排泄和抑制PI3K/AKT/NF-κB信号通路预防HN小鼠的肾损伤、炎症和纤维化。
