Traditional Chinese Medicine Department, the Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China.
Traditional Chinese Medicine Department, the Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China.
Life Sci. 2018 Aug 1;206:77-83. doi: 10.1016/j.lfs.2018.05.037. Epub 2018 May 22.
Apoptosis of podocytes plays a crucial role in diabetic nephropathy (DN) development, and astragaloside (AS-IV) has a significant impact on podocyte apoptosis. This study aims to explore the effect of AS-IV on diabetic nephropathy progression.
The diabetic nephropathy model was established in rats with streptozotocin (STZ) injection. The albuminuria was examined by using the enzyme linked immunosorbent assay (ELISA). The expression of miR-378, tumor-necrosis factor (TNF) receptor (TNFR)-associated factor 5 (TRAF5) mRNA and protein was analyzed by qRT-PCR and western blot, respectively. Cell transfection was conducted for modulating endogenous expression of miR-378. Dual luciferase reporter assay was used to evaluate the interaction between miR-378 and TRAF5. The terminal deoxynucleotidy transferase dUTP nick end labeling (TUNEL) staining assay was performed for apoptosis detection.
AS-IV protected diabetic rats from developing into diabetic nephropathy. The expression of miR-378 was down-regulated in diabetic nephropathy rats, which was reversed by AS-IV. AS-IV enhanced the expression of miR-378 in podocytes treated with high glucose. MiR-378 negatively regulated TRAF5. AS-IV inhibited the expression of TRAF5 through miR-378. AS-IV suppressed apoptosis of podocytes via targeting miR-378.
AS-IV suppresses apoptosis of the podocytes through the miR-378/TRAF5 signaling pathway, and thereby repressing diabetic nephropathy development.
足细胞凋亡在糖尿病肾病（DN）的发生发展中起着关键作用，而黄芪甲苷（AS-IV）对足细胞凋亡有显著影响。本研究旨在探讨 AS-IV 对糖尿病肾病进展的影响。
采用链脲佐菌素（STZ）注射建立糖尿病肾病大鼠模型。通过酶联免疫吸附试验（ELISA）检测白蛋白尿。采用 qRT-PCR 和 Western blot 分别分析 miR-378、肿瘤坏死因子（TNF）受体（TNFR）相关因子 5（TRAF5）mRNA 和蛋白的表达。通过细胞转染调节内源性 miR-378 的表达。采用双荧光素酶报告基因实验评估 miR-378 与 TRAF5 的相互作用。采用末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）染色法检测细胞凋亡。
AS-IV 可防止糖尿病大鼠发生糖尿病肾病。糖尿病肾病大鼠中 miR-378 的表达下调，AS-IV 可使其逆转。AS-IV 增强了高糖处理的足细胞中 miR-378 的表达。miR-378 负调控 TRAF5。AS-IV 通过 miR-378 抑制 TRAF5 的表达。AS-IV 通过靶向 miR-378 抑制足细胞凋亡。
AS-IV 通过 miR-378/TRAF5 信号通路抑制足细胞凋亡，从而抑制糖尿病肾病的发生发展。
