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Abstract：
BACKGROUND: Nephrotic syndrome(NS) has emerged as a worldwide public health problem. Renal fibrosis is the most common pathological change from NS to end-stage renal failure, seriously affecting the prognosis of renal disease. Although tremendous efforts have been made to treat NS, specific drug therapies to delay the progression of NS toward end-stage renal failure are limited. Epimedium is generally used to treat kidney disease in traditional Chinese medicine. Icariin is a principal active component of Epimedium.
METHODS: We used Sprague Dawley rats to establish NS models by injecting doxorubicin through the tail vein. Then icariin and prednisone were intragastric administration. Renal function was examined by an automatic biochemical analyzer. Pathology of the kidney was detected by Hematoxylin-Eosin and Masson staining respectively. Furthermore, RT-PCR, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Western Blot and Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling staining were employed to detect the proteins related to pyroptosis and EMT. HK-2 cells exposed to doxorubicin were treated with icariin, and cell viability was assessed using the MTT. EMT was assessed using Enzyme-Linked Immunosorbent Assay and Western Blot.
RESULTS: The study showed that icariin significantly improved renal function and renal fibrosis in rats. In addition, icariin effectively decreased NOD-like receptor thermal protein domain associated protein 3,Caspase-1, Gasdermin D, Ly6C, and interleukin (IL)-1β. Notably, treatment with icariin also inhibited the levels of TGF-β, α-SMA and E-cadherin.
CONCLUSIONS: It is confirmed that icariin can improve renal function and alleviate renal fibrosis by inhibiting pyroptosis and the mechanism may be related to epithelial-to-mesenchymal transition. Icariin treatment might be recommended as a new approach for NS.
METHODS: We used Sprague Dawley rats to establish NS models by injecting doxorubicin through the tail vein. Then icariin and prednisone were intragastric administration. Renal function was examined by an automatic biochemical analyzer. Pathology of the kidney was detected by Hematoxylin-Eosin and Masson staining respectively. Furthermore, RT-PCR, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Western Blot and Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling staining were employed to detect the proteins related to pyroptosis and EMT. HK-2 cells exposed to doxorubicin were treated with icariin, and cell viability was assessed using the MTT. EMT was assessed using Enzyme-Linked Immunosorbent Assay and Western Blot.
RESULTS: The study showed that icariin significantly improved renal function and renal fibrosis in rats. In addition, icariin effectively decreased NOD-like receptor thermal protein domain associated protein 3,Caspase-1, Gasdermin D, Ly6C, and interleukin (IL)-1β. Notably, treatment with icariin also inhibited the levels of TGF-β, α-SMA and E-cadherin.
CONCLUSIONS: It is confirmed that icariin can improve renal function and alleviate renal fibrosis by inhibiting pyroptosis and the mechanism may be related to epithelial-to-mesenchymal transition. Icariin treatment might be recommended as a new approach for NS.
摘要：
背景：肾病综合征（NS）已成为全球公共卫生问题。肾纤维化是从NS到终末期肾衰竭最常见的病理变化，严重影响肾脏疾病的预后。尽管已经做出了巨大的努力来治疗NS，延迟NS进展为终末期肾衰竭的特定药物治疗是有限的.淫羊藿一般用于治疗肾脏病的中药。淫羊藿苷是淫羊藿的主要活性成分。
方法：采用SD大鼠尾静脉注射阿霉素建立NS模型。然后灌胃淫羊藿苷和泼尼松。通过自动生化分析仪检查肾功能。分别通过苏木精-伊红和Masson染色检测肾脏的病理学。此外，RT-PCR,酶联免疫吸附测定，免疫组织化学,Western印迹和末端脱氧核苷酸转移酶介导的尼克末端标记染色用于检测与焦亡和EMT相关的蛋白。用淫羊藿苷处理暴露于阿霉素的HK-2细胞，并且使用MTT评估细胞活力。使用酶联免疫吸附测定和Western印迹评估EMT。
结果：研究表明淫羊藿苷可明显改善大鼠肾功能和肾纤维化。此外,淫羊藿苷有效降低NOD样受体热蛋白结构域相关蛋白3、Caspase-1、GasderminD、Ly6C,和白细胞介素(IL)-1β。值得注意的是,淫羊藿苷治疗也抑制了TGF-β的水平，α-SMA和E-钙粘蛋白。
结论：淫羊藿苷可通过抑制细胞凋亡改善肾功能，减轻肾纤维化，其机制可能与上皮间质转化有关。淫羊藿苷治疗可能被推荐为NS的新方法。
方法：采用SD大鼠尾静脉注射阿霉素建立NS模型。然后灌胃淫羊藿苷和泼尼松。通过自动生化分析仪检查肾功能。分别通过苏木精-伊红和Masson染色检测肾脏的病理学。此外，RT-PCR,酶联免疫吸附测定，免疫组织化学,Western印迹和末端脱氧核苷酸转移酶介导的尼克末端标记染色用于检测与焦亡和EMT相关的蛋白。用淫羊藿苷处理暴露于阿霉素的HK-2细胞，并且使用MTT评估细胞活力。使用酶联免疫吸附测定和Western印迹评估EMT。
结果：研究表明淫羊藿苷可明显改善大鼠肾功能和肾纤维化。此外,淫羊藿苷有效降低NOD样受体热蛋白结构域相关蛋白3、Caspase-1、GasderminD、Ly6C,和白细胞介素(IL)-1β。值得注意的是,淫羊藿苷治疗也抑制了TGF-β的水平，α-SMA和E-钙粘蛋白。
结论：淫羊藿苷可通过抑制细胞凋亡改善肾功能，减轻肾纤维化，其机制可能与上皮间质转化有关。淫羊藿苷治疗可能被推荐为NS的新方法。
