Abstract：
BACKGROUND: Herba epimedium brevicornu maxim is traditionally known as a sexual enhancement, and has the effect of tonifying kidney yang. Icariin is a flavonoid extracted from epimedium brevicornu maxim, and has been shown to improve nephropathy disease.
OBJECTIVE: This study investigated the possible role of icariin in regulating renal EndMT in type 2 diabetic nephropathy (T2DN).
METHODS: Male type 2 diabetic Sprague Dawley rats, Male D2.BKS(D)-Leprdb/J (db/db) mice, and mouse glomerular endothelial cells were utilized to evaluate the effect of icariin. Western blotting, Q-PCR, immunohistochemistry, H&E, Masson staining, immunofluorescence, and siRNA transfection, were performed in this study.
RESULTS: The inhibitory function of icariin in renal fibrosis and renal EndMT was verified in type 2 diabetic animals. Methyltestosterone suppressed renal fibrosis and EndMT in db/db mice. Androgen receptor (AR), the major receptor of testosterone, was upregulated by icariin. The AR antagonist MDV3100, blocked the inhibition by icariin in renal EndMT, revealing that icariin repressed renal EndMT by activating AR. In addition, icariin and methyltestosterone upregulated the Raf kinase inhibitor protein (RKIP) in db/db mice. Furthermore, siRNA-RKIP inhibited the effect of icariin on EndMT. The MEK/ERK pathway, as the downstream pathway of RKIP, was suppressed by icariin and methyltestosterone. Of note, the effect of icariin on the MEK/ERK pathway was abolished by MDV3100 or siRNA-RKIP.
CONCLUSIONS: These results supported that icariin targeted AR/RKIP/MEK/ERK pathway to suppress renal fibrosis and EndMT in T2DN.
OBJECTIVE: This study investigated the possible role of icariin in regulating renal EndMT in type 2 diabetic nephropathy (T2DN).
METHODS: Male type 2 diabetic Sprague Dawley rats, Male D2.BKS(D)-Leprdb/J (db/db) mice, and mouse glomerular endothelial cells were utilized to evaluate the effect of icariin. Western blotting, Q-PCR, immunohistochemistry, H&E, Masson staining, immunofluorescence, and siRNA transfection, were performed in this study.
RESULTS: The inhibitory function of icariin in renal fibrosis and renal EndMT was verified in type 2 diabetic animals. Methyltestosterone suppressed renal fibrosis and EndMT in db/db mice. Androgen receptor (AR), the major receptor of testosterone, was upregulated by icariin. The AR antagonist MDV3100, blocked the inhibition by icariin in renal EndMT, revealing that icariin repressed renal EndMT by activating AR. In addition, icariin and methyltestosterone upregulated the Raf kinase inhibitor protein (RKIP) in db/db mice. Furthermore, siRNA-RKIP inhibited the effect of icariin on EndMT. The MEK/ERK pathway, as the downstream pathway of RKIP, was suppressed by icariin and methyltestosterone. Of note, the effect of icariin on the MEK/ERK pathway was abolished by MDV3100 or siRNA-RKIP.
CONCLUSIONS: These results supported that icariin targeted AR/RKIP/MEK/ERK pathway to suppress renal fibrosis and EndMT in T2DN.
摘要：
背景：淫羊藿传统上被称为性增强，有补肾阳气的功效。淫羊藿苷是从淫羊藿中提取的类黄酮，并已被证明可以改善肾病。
目的：本研究探讨淫羊藿苷在2型糖尿病肾病（T2DN）中对肾脏EndMT的调节作用。
方法：雄性2型糖尿病SD大鼠,男性D2.BKS(D)-Leprdb/J(db/db)小鼠,和小鼠肾小球内皮细胞用于评估淫羊藿苷的效果。西方印迹,Q-PCR,免疫组织化学，H&E,Masson染色,免疫荧光，和siRNA转染，在这项研究中进行。
结果：淫羊藿苷对2型糖尿病动物肾脏纤维化和肾脏EndMT的抑制作用得到证实。甲基睾酮抑制db/db小鼠的肾纤维化和EndMT。雄激素受体(AR),睾酮的主要受体，被淫羊藿苷上调。AR拮抗剂MDV3100，阻断淫羊藿苷对肾脏EndMT的抑制作用，揭示淫羊藿苷通过激活AR抑制肾脏EndMT。此外,淫羊藿苷和甲基睾酮上调db/db小鼠中的Raf激酶抑制剂蛋白(RKIP)。此外，siRNA-RKIP抑制淫羊藿苷对EndMT的作用。MEK/ERK通路,作为RKIP的下游途径，被淫羊藿苷和甲基睾酮抑制。值得注意的是，淫羊藿苷对MEK/ERK通路的影响被MDV3100或siRNA-RKIP消除.
结论：这些结果支持淫羊藿苷靶向AR/RKIP/MEK/ERK途径抑制T2DN的肾纤维化和EndMT。
目的：本研究探讨淫羊藿苷在2型糖尿病肾病（T2DN）中对肾脏EndMT的调节作用。
方法：雄性2型糖尿病SD大鼠,男性D2.BKS(D)-Leprdb/J(db/db)小鼠,和小鼠肾小球内皮细胞用于评估淫羊藿苷的效果。西方印迹,Q-PCR,免疫组织化学，H&E,Masson染色,免疫荧光，和siRNA转染，在这项研究中进行。
结果：淫羊藿苷对2型糖尿病动物肾脏纤维化和肾脏EndMT的抑制作用得到证实。甲基睾酮抑制db/db小鼠的肾纤维化和EndMT。雄激素受体(AR),睾酮的主要受体，被淫羊藿苷上调。AR拮抗剂MDV3100，阻断淫羊藿苷对肾脏EndMT的抑制作用，揭示淫羊藿苷通过激活AR抑制肾脏EndMT。此外,淫羊藿苷和甲基睾酮上调db/db小鼠中的Raf激酶抑制剂蛋白(RKIP)。此外，siRNA-RKIP抑制淫羊藿苷对EndMT的作用。MEK/ERK通路,作为RKIP的下游途径，被淫羊藿苷和甲基睾酮抑制。值得注意的是，淫羊藿苷对MEK/ERK通路的影响被MDV3100或siRNA-RKIP消除.
结论：这些结果支持淫羊藿苷靶向AR/RKIP/MEK/ERK途径抑制T2DN的肾纤维化和EndMT。
