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抗纤灵汤对转化生长因子-1/信号转导和转录激活因子及细胞外基质沉积表达的影响

Effect of Kangxianling Decoction on Expression of TGF-1/Smads and Extracellular Matrix Deposition.

作者信息

Ji Jing, He Liqun

机构信息

Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

Evid Based Complement Alternat Med. 2019 Jan 1;2019:5813549. doi: 10.1155/2019/5813549. eCollection 2019.

Abstract

Kangxianling (KXL) decoction is a traditional Chinese herbal formulation which has been used to treat early and midterm chronic renal failure. Renal fibrosis is a common characteristic of progressive chronic kidney diseases (CKD). The formation of renal fibrosis is caused by kidney trauma, infection, and immune response. The pathophysiological mechanism of renal fibrosis was mainly due to increased collagen synthesis in the kidney, decreased degradation, and a large amount of extracellular matrix (ECM) deposition. The purpose of this study was intended to evaluate the effect of Kangxianling decoction on expression of TGF-1/Smad signaling pathway in renal fibrosis rats. 50 specific pathogen-free Sprague Dawley (SPF SD) rats were randomly divided into five groups: control group, sham group, 5/6 nephrectomy model group, 5/6 nephrectomy model plus KXL decoction (21g /kg) group, and 5/6 nephrectomy model plus Losartan Potassium (LP) (33.3 g/kg) group. The rats were all sacrificed after two months and the left kidney tissue was sampled. HE staining was used to observe the renal pathological changes and the score of kidney damage was made. Masson staining was used to observe the degree of renal fibrosis. Immunohistochemical staining, western blot, and qRT-PCR were used to detect the expression levels of related molecules in TGF-1/Smad signaling pathway. The results suggested that KXL could lighten renal histopathology damage, downregulate the expression of TGF-1 (transforming growth factor-1), Smad2/3, CTGF (connective tissue growth factor), Collagen I, and Collagen III, and upregulate the expression level of Smad7.

摘要

康肾灵(KXL)汤剂是一种传统的中药配方,一直用于治疗早中期慢性肾衰竭。肾纤维化是进行性慢性肾脏病(CKD)的一个共同特征。肾纤维化的形成是由肾脏创伤、感染和免疫反应引起的。肾纤维化的病理生理机制主要是由于肾脏中胶原蛋白合成增加、降解减少以及大量细胞外基质(ECM)沉积。本研究的目的是评估康肾灵汤剂对肾纤维化大鼠TGF-1/Smad信号通路表达的影响。将50只无特定病原体的Sprague Dawley(SPF SD)大鼠随机分为五组:对照组、假手术组、5/6肾切除模型组、5/6肾切除模型加KXL汤剂(21g /kg)组和5/6肾切除模型加氯沙坦钾(LP)(33.3 g/kg)组。两个月后处死大鼠并采集左肾组织样本。采用HE染色观察肾脏病理变化并进行肾损伤评分。采用Masson染色观察肾纤维化程度。采用免疫组织化学染色、蛋白质免疫印迹法和qRT-PCR检测TGF-1/Smad信号通路相关分子的表达水平。结果表明,KXL可减轻肾脏组织病理学损伤,下调TGF-1(转化生长因子-1)、Smad2/3、结缔组织生长因子(CTGF)、I型胶原蛋白和III型胶原蛋白的表达,并上调Smad7的表达水平。

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