Huayu Tongmai Granules protects against vascular endothelial dysfunction via up-regulating miR-185 and down-regulating RAGE.

OBJECTIVE: Receptor of advanced glycation end products (AGE) is a membrane protein that contribute to the initiation and progression of diabetic vascular complications, which is reported as a target of miR-185. Huayu Tongmai Granules are a Chinese herbal compound that is capable of treating diabetic angiopathy. This study was designed to explore the molecular biological mechanism by which Huayu Tongmai Granules protect against diabetic angiopathy. Methods 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 (qRT-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 cells (HUVECs) line. Additionally, the protein levels of RAGE or Bax were determined using western blotting. Cell apoptosis was determined by Terminal dUTP nick-end labelling (TUNEL) assay or flow cytometry. Results In this study, we found that Huayu Tongmai Granules significantly decreased blood glucose and serum ROS and upregulated serum NO concentration. MiR-185 was low-expressed in diabetic rats, however, Huayu Tongmai Granules intervention upregulated miR-185. Stable overexpression of miR-185 directly suppressed the expression of RAGE and further suppressed endothelial cell apoptosis. Conclusion Huayu Tongmai Granules appear to have a therapeutic effect on diabetic angiopathy that is most likely mediated by miR-185/RAGE axis.