State Key Laboratory of Natural and Biomimetic Drugs, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Department of Pharmacology, School of Basic Medical Sciences, Peking University, 100191, P.R. China.
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, P.R. China.
Sci Rep. 2016 Aug 22;6:31759. doi: 10.1038/srep31759.
Albuminuria is a causative and aggravating factor for progressive renal damage in chronic kidney disease (CKD). The aim of this study was to determine if low molecular weight fucoidan (LMWF) could protect renal function and tubular cells from albumin overload caused injury. Treatment with 10 mg/g bovine serum albumin caused renal dysfunction, morphological changes, and overexpression of inflammation and fibrosis associated proteins in 129S2/Sv mice. LMWF (100 mg/kg) protected against kidney injury and renal dysfunction with decreased blood creatinine by 34% and urea nitrogen by 25%, increased creatinine clearance by 48%, and decreased significantly urinary albumin concentration. In vitro proximal tubule epithelial cell (NRK-52E) model showed that LMWF dose-dependently inhibited overexpression of proinflammatory and profibrotic factors, oxidative stress and apoptosis caused by albumin overload. These experimental results indicate that LMWF protects against albumin overload caused renal injury by inhibiting inflammation, fibrosis, oxidative stress and apoptosis, which suggests that LMWF could be a promising candidate drug for preventing CKD.
蛋白尿是慢性肾脏病（CKD）进行性肾损伤的病因和加重因素。本研究旨在确定低分子量岩藻聚糖硫酸酯（LMWF）是否可以保护肾功能和肾小管细胞免受白蛋白过载引起的损伤。用 10mg/g 牛血清白蛋白处理导致 129S2/Sv 小鼠肾功能障碍、形态改变以及炎症和纤维化相关蛋白表达过度。LMWF（100mg/kg）通过降低 34%的血肌酐和 25%的尿素氮、增加 48%的肌酐清除率来预防肾损伤和肾功能障碍，同时显著降低尿白蛋白浓度。体外近端肾小管上皮细胞（NRK-52E）模型表明，LMWF 呈剂量依赖性抑制白蛋白过载引起的促炎和促纤维化因子、氧化应激和细胞凋亡的过度表达。这些实验结果表明，LMWF 通过抑制炎症、纤维化、氧化应激和细胞凋亡来防止白蛋白过载引起的肾损伤，这表明 LMWF 可能是预防 CKD 的有前途的候选药物。
