Effect of diabetes blood-stasis syndrome and Xuefu Zhuyu decoction on ERK1/2-VEGF signal pathway in rat retina Müller cells

Histol Histopathol. 2022 Aug;37(8):757-767. doi: 10.14670/HH-18-427. Epub 2022 Feb 3.

Abstract

Aims: This research was aimed to investigate whether diabetic blood-stasis syndrome had a relationship with ERK1/2-VEGF signaling pathway in rat retina Müller cells and Traditional Chinese Drugs designed for promoting blood circulation to remove blood stasis had effectiveness for diabetic retinopathy (DR) treatment.

Methods: Immunofluorescence was applied to determine purity of Müller cells. Müller cells were stimulated by blood serum obtained from rats with blood-stasis syndrome and then treated by Xuefu Zhuyu decoction. Western blot analysis, RT-PCR and ELISA were used to measure the expression of VEGF. Western blot analysis was used to determine the phosphorylation of ERK1/2. The status of AP-1 DNA binding activity was monitored by electrophoretic mobility shift assay (EMSA).

Results: Stimulation of Müller cells by blood serum of rat with diabetic blood stasis increased the secretion of VEGF, activated ERK1/2 and AP-1 DNA-binding activity. And treatment of Xuefu Zhuyu decoction could weaken this phenomenon. What's more, ERK1/2 signaling pathway inhibitor U0126 also could inhibit the expression of VEGF.

Conclusions: Diabetic blood-stasis syndrome in theory of traditional Chinese Medicine has positive role in regulating ERK1/2-VEGF signaling pathway. Traditional Chinese drugs for promoting blood circulation to remove blood stasis would be an effective therapy to treat DR.

MeSH terms

  • Animals
  • DNA / metabolism
  • Diabetes Mellitus*
  • Diabetic Retinopathy* / drug therapy
  • Diabetic Retinopathy* / metabolism
  • Drugs, Chinese Herbal
  • Ependymoglial Cells
  • MAP Kinase Signaling System
  • Rats
  • Retina
  • Signal Transduction / physiology
  • Transcription Factor AP-1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Drugs, Chinese Herbal
  • Transcription Factor AP-1
  • Vascular Endothelial Growth Factor A
  • Xue-Fu-Zhu-Yu decoction
  • DNA