Doctor Candidates of 2014 Grade, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
Department of Geriatric, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
Biosci Rep. 2018 Nov 30;38(6). doi: 10.1042/BSR20180674. Print 2018 Dec 21.
: Receptor of advanced glycation end products (RAGE) is a membrane protein that contributes to the initiation and progression of diabetic vascular complications, which is reported as a target of miR-185. Huayu Tongmai Granules is a Chinese herbal compound that is capable of treating diabetic angiopathy. The present study was designed to explore the molecular biological mechanism by which Huayu Tongmai Granules protects against diabetic angiopathy. The rat model of diabetes and hyperglucose cell model were established. The blood glucose was detected to verify whether the model was successfully established. Besides, serum nitric oxide (NO) and reactive oxygen species (ROS) concentrations of the rats in each group were determined. The quantitative real-time PCR analysis was performed to examine the mRNA expression levels of miR-185 and other miRNAs in femoral artery of rats or human umbilical vein endothelial cell line. Additionally, the protein levels of RAGE or Bax were determined using Western blotting. Cell apoptosis was determined by terminal dUTP nick-end labeling assay or flow cytometry. In the present study, we found that Huayu Tongmai Granules significantly decreased blood glucose and serum ROS and up-regulated serum NO concentration. MiR-185 was low-expressed in diabetic rats; however, Huayu Tongmai Granules intervention up-regulated miR-185. Stable overexpression of miR-185 directly suppressed the expression of RAGE and further suppressed endothelial cell apoptosis.: Huayu Tongmai Granules appears to have a therapeutic effect on diabetic angiopathy that is most probably mediated by miR-185/RAGE axis.
: 晚期糖基化终产物受体 (RAGE) 是一种膜蛋白，它有助于糖尿病血管并发症的发生和发展，被报道为 miR-185 的靶点。化瘀通脉颗粒是一种中药复方，能够治疗糖尿病血管病变。本研究旨在探讨化瘀通脉颗粒防治糖尿病血管病变的分子生物学机制。建立糖尿病大鼠模型和高糖细胞模型，检测血糖以验证模型是否成功建立。此外，还测定了各组大鼠血清中一氧化氮（NO）和活性氧（ROS）的浓度。采用实时定量 PCR 分析检测大鼠股动脉或人脐静脉内皮细胞系中 miR-185 和其他 miRNA 的 mRNA 表达水平。此外，还采用 Western blot 检测 RAGE 或 Bax 蛋白水平。采用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法或流式细胞术检测细胞凋亡。本研究发现，化瘀通脉颗粒可显著降低血糖和血清 ROS 水平，升高血清 NO 浓度。糖尿病大鼠 miR-185 低表达，化瘀通脉颗粒干预后 miR-185 上调。miR-185 的稳定过表达直接抑制 RAGE 的表达，并进一步抑制内皮细胞凋亡。化瘀通脉颗粒对糖尿病血管病变可能具有治疗作用，其作用机制可能与 miR-185/RAGE 轴有关。
