Yang Liuyi, Wang Meng, Zhou Yuan, Yang Jing, Ye Chaoyang, Wang Chen
Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Evid Based Complement Alternat Med. 2021 Jun 7;2021:5539584. doi: 10.1155/2021/5539584. eCollection 2021.
Renal interstitial fibrosis is a pathological manifestation of progression of chronic kidney disease induced by various factors. Shen Shuai II Recipe (SSR) has been used in clinical practice for more than 20 years, and clinical studies have confirmed that SSR significantly improves the renal function of patients with chronic kidney disease. However, the specific mechanisms underlying its efficacy require further research. This study aims to explore the influencing factors of renal interstitial fibrosis in the context of hypoxia via the IL-1/ pathway and the potential molecular mechanisms of SSR intervention in vivo and in vitro.
A rat model of chronic renal failure was developed by performing 5/6 (ablation/infarction, A/I) surgery on randomly selected, male Sprague Dawley rats. Thirty-six successfully modeled rats were randomly divided into three groups: 5/6 (A/I), 5/6 (A/I) + SSR, and 5/6 (A/I) + losartan. Another 12 rats were used as the sham group. After 8 weeks of the corresponding intervention, renal function, liver function, and protein expression of renal-fibrosis-related factors, HIF-1, IL-1, and , were detected. In vitro analysis was performed using hypoxia-induced rat renal tubular epithelial cells (NRK-52E) and IL-1-stimulated rat renal interstitial fibroblasts (NRK-49F). IL-1 concentration in the culture medium and IL-1 protein expression in hypoxic NRK-52E treated with different concentrations of SSR were investigated. Furthermore, we also studied the changes in protein expression of and fibrosis-related factors after gene silencing in IL-1-stimulated NRK-49F treated with SSR.
Shen Shuai II Recipe significantly reduced RIF and downregulated the expression of HIF-1, , and IL-1 proteins in 5/6 (A/I) rats with chronic renal failure. It also inhibited IL-1 secretion from NRK-52E induced by hypoxia, which in turn inhibited fibroblast activation mediated by the IL-1/ pathway, and finally reduced the overproduction of the extracellular matrix.
The renoprotective effects of SSR in rats with chronic renal failure may be related to its inhibition of hypoxia via the IL-1/ pathway. Thus, SSR is a potentially effective drug for delaying the progression of renal interstitial fibrosis.
肾间质纤维化是各种因素诱导的慢性肾脏病进展的病理表现。肾衰Ⅱ号方（SSR）已在临床应用20余年，临床研究证实其能显著改善慢性肾脏病患者的肾功能。然而，其疗效的具体机制尚需进一步研究。本研究旨在探讨缺氧条件下通过白细胞介素-1（IL-1）/信号通路影响肾间质纤维化的因素以及SSR体内外干预的潜在分子机制。
对随机选取的雄性Sprague Dawley大鼠行5/6肾切除（切除/梗死，A/I）手术建立慢性肾衰竭大鼠模型。将36只成功建模的大鼠随机分为三组：5/6（A/I）组、5/6（A/I）+SSR组和5/6（A/I）+氯沙坦组。另取12只大鼠作为假手术组。经过8周相应干预后，检测肾功能、肝功能及肾纤维化相关因子、缺氧诱导因子-1（HIF-1）、IL-1及（此处原文缺失相关因子名称）的蛋白表达。采用缺氧诱导的大鼠肾小管上皮细胞（NRK-52E）和IL-1刺激的大鼠肾间质成纤维细胞（NRK-49F）进行体外分析。研究不同浓度SSR处理缺氧NRK-52E后培养基中IL-1浓度及IL-1蛋白表达情况。此外，还研究了在SSR处理的IL-1刺激的NRK-49F中（此处原文缺失相关基因名称）基因沉默后（此处原文缺失相关因子名称）及纤维化相关因子蛋白表达的变化。
肾衰Ⅱ号方能显著减轻5/6肾切除慢性肾衰竭大鼠的肾间质纤维化，下调HIF-1、（此处原文缺失相关因子名称）及IL-1蛋白表达。它还抑制缺氧诱导的NRK-52E分泌IL-1，进而抑制IL-1/信号通路介导的成纤维细胞活化，最终减少细胞外基质的过度产生。
肾衰Ⅱ号方对慢性肾衰竭大鼠的肾脏保护作用可能与其通过IL-1/信号通路抑制缺氧有关。因此，肾衰Ⅱ号方是一种潜在的延缓肾间质纤维化进展的有效药物。
