Department of Nephrology, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Changhai Hospital, Second Military Medical University, Shanghai, China.
Pharm Biol. 2020 Dec;58(1):1115-1122. doi: 10.1080/13880209.2020.1844241.
Nephrolithiasis is a major public health problem worldwide and Fu-Fang-Jin-Qian-Cao granules (FFJQC) is a traditional Chinese herbal formula that is used to treat nephrolithiasis. The main component of nephrolithiasis is calcium oxalate (CaOx) and the epithelial-mesenchymal transition (EMT) shown to play a crucial role in CaOx-induced kidney injury. However, the mechanism underlying the therapeutic effect of FFJQC on the CaOx-induced renal EMT is unknown.
This study explores the therapeutic benefits and mechanism of FFJQC in oxalate-induced kidney injury.
60 male C57BL/6 mice were used in this experiment and divided into 6 groups. A mouse kidney stone model was created by intraperitoneal injection of glyoxylate at a dose of 100 mg/kg for 6 days. The standardized FFJQC was used to treat mouse crystal kidney injury by gavage at 1.35 and 2.7 g/kg, respectively. Western blotting and immunostaining for E-cadherin, cytokeratin 18 (CK18), vimentin, smooth muscle α-actin (α-SMA) and transforming growth factor β (TGF-β)/Smad pathway were conducted on renal tissues.
Following CaOx-induced kidney injury, the levels of E-cadherin and CK18 in kidney decreased, while vimentin and α-SMA levels increased. The FFJQC treatment increased the levels of E-cadherin and CK18 and decreased vimentin and α-SMA levels in varying degrees. What's more, the FFJQC reduced the expression of CaOx-induced fibrosis marker collagen II.
FFJQC alleviated the CaOx-induced renal EMT and fibrosis by regulating TGF-β/smad pathway. Therefore, the FFJQC is an important traditional Chinese medicine for the treatment of CaOx-induced renal injury and fibrosis.
肾结石是全球范围内的一个主要公共卫生问题,复方金钱草颗粒(FFJQC)是一种用于治疗肾结石的中药方剂。肾结石的主要成分是草酸钙(CaOx),上皮-间充质转化(EMT)被证明在 CaOx 诱导的肾损伤中起着关键作用。然而,FFJQC 治疗 CaOx 诱导的肾 EMT 的机制尚不清楚。
本研究探讨 FFJQC 治疗草酸钙诱导肾损伤的疗效及其机制。
本实验使用 60 只雄性 C57BL/6 小鼠,分为 6 组。通过腹腔注射草酸盐(剂量为 100mg/kg),连续 6 天,建立小鼠肾结石模型。通过灌胃分别给予 1.35 和 2.7g/kg 的标准化 FFJQC 治疗小鼠晶体肾损伤。对肾脏组织进行 E-钙黏蛋白、细胞角蛋白 18(CK18)、波形蛋白、平滑肌α-肌动蛋白(α-SMA)和转化生长因子β(TGF-β)/Smad 通路的 Western 印迹和免疫染色。
在 CaOx 诱导的肾损伤后,肾脏中 E-钙黏蛋白和 CK18 的水平降低,而波形蛋白和α-SMA 的水平升高。FFJQC 治疗在不同程度上增加了 E-钙黏蛋白和 CK18 的水平,降低了波形蛋白和α-SMA 的水平。此外,FFJQC 降低了 CaOx 诱导的纤维化标志物胶原 II 的表达。
FFJQC 通过调节 TGF-β/smad 通路缓解了 CaOx 诱导的肾 EMT 和纤维化。因此,FFJQC 是治疗 CaOx 诱导的肾损伤和纤维化的重要中药方剂。