Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Department of Nephrology, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China.
Biosci Rep. 2019 Feb 22;39(2). doi: 10.1042/BSR20181833. Print 2019 Feb 28.
Nephrolithiasis is one of the world's major public health burdens with a high incidence and a risk of persistent renal dysfunction. Fu-Fang-Jin-Qian-Chao granules (FFJQC), a traditional Chinese herb formula, is commonly used in treatment of nephrolithiasis. However, the therapeutic mechanism of FFJQC on kidney stone has still been a mystery. The objective of the present study is to explore the therapeutic mechanism of FFJQC on kidney injury and identify unique metabolomics patterns using a mouse model of kidney stone induced by a calcium oxalate (CaOx) deposition. Von Kossa staining and immuno-histopathological staining of osteopontin (OPN), cluster of differentiation 44 (CD44) and calbindin-D28k were conducted on renal sections. Biochemical analysis was performed on serum, urine, and kidney tissues. A metabolomics approach based on ultra-HPLC coupled with quadrupole-TOF-MS (UHPLC-Q-TOF/MS) was used for serum metabolic profiling. The immunohistopathological and biochemical analysis showed the therapeutic benefits of FFJQC. The expression levels of OPN and CD44 were decreased while calbindin-D28k increased after the CaOx injured mice were treated with FFJQC. In addition, total of 81 serum metabolites were identified to be associated with protective effects of FFJQC on CaOx crystal injured mice. Most of these metabolites were involved in purine, amino acid, membrane lipid and energy metabolism. Potential metabolite biomarkers were found for CaOx crystal-induced renal damage. Potential metabolite biomarkers of CaOx crystal-induced renal damage were found. FFJQC shows therapeutic benefits on CaOx crystal injured mice via regulation of multiple metabolic pathways including amino acids, purine, pyrimidine, glycerolipid, arachidonic acid (AA), sphingolipid, glycerophospholipid, and fatty acid.
肾结石是全球主要的公共卫生负担之一，其发病率高，并存在持续性肾功能障碍的风险。复方金钱草颗粒（FFJQC）是一种中药方剂，常用于治疗肾结石。然而，FFJQC 治疗肾结石的确切机制仍不清楚。本研究旨在通过草酸钙（CaOx）沉积诱导的小鼠肾结石模型，探讨 FFJQC 对肾损伤的治疗机制，并确定独特的代谢组学模式。对肾组织进行 Von Kossa 染色和骨桥蛋白（OPN）、CD44 及钙结合蛋白-D28k 的免疫组织化学染色。对血清、尿液和肾脏组织进行生化分析。采用基于超高效液相色谱-四极杆飞行时间质谱联用（UHPLC-Q-TOF/MS）的代谢组学方法进行血清代谢谱分析。免疫组织化学和生化分析表明 FFJQC 具有治疗作用。用 FFJQC 治疗 CaOx 损伤的小鼠后，OPN 和 CD44 的表达水平降低，而 calbindin-D28k 增加。此外，共鉴定出 81 种与 FFJQC 对 CaOx 晶体损伤小鼠保护作用相关的血清代谢物。这些代谢物大多与嘌呤、氨基酸、膜脂和能量代谢有关。发现了潜在的与 FFJQC 对 CaOx 晶体损伤小鼠保护作用相关的代谢物生物标志物。FFJQC 通过调节包括氨基酸、嘌呤、嘧啶、甘油磷脂、花生四烯酸（AA）、鞘脂、甘油磷脂和脂肪酸在内的多种代谢途径，对 CaOx 晶体损伤的小鼠具有治疗作用。
