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复方金钱草颗粒通过抑制 TGF-β/smad 通路防治草酸钙诱导的肾 EMT。

Fu-Fang-Jin-Qian-Cao herbal granules protect against the calcium oxalate-induced renal EMT by inhibiting the TGF-β/smad pathway.

机构信息

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.

出版信息

Pharm Biol. 2020 Dec;58(1):1115-1122. doi: 10.1080/13880209.2020.1844241.

Abstract

CONTEXT

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.

OBJECTIVE

This study explores the therapeutic benefits and mechanism of FFJQC in oxalate-induced kidney injury.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

目的

本研究探讨 FFJQC 治疗草酸钙诱导肾损伤的疗效及其机制。

材料和方法

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。

结果

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8974/7671650/14e7a0873918/IPHB_A_1844241_F0001_C.jpg

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