[Effects of ELK-1/JNK/c-Fos on apoptosis of rat hippocampal neurons cultured in vitro with Zuogui Jiangtang Jieyu Formula in simulated diabetes mellitus complicated with depression]

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2019 Jan;35(1):50-54. doi: 10.12047/j.cjap.5703.2019.013.
[Article in Chinese]

Abstract

Objective: To study the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF, the Chinese Medicine) on hippocampal neuron apoptosis in diabetes mellitus complicated with depression (DD).

Methods: The primary cultured hippocampal neurons were treated with high glucose (150 mmol/L) and corticosterone (200 micromol/L) to establish the cell model of DD in vitro. The cultured hippocampal neurons were randomly divided into five groups: blank serum group, normal group, Zuogui Jiangtang Jieyu recipe drug-containing serum group, positive drug (metformin + fluoxetine) drug-containing serum group and model group (three compound holes in each group). The model group and the normal group were given the same amount of culture medium, and the other groups were given the corresponding serum with 10% volume fraction for 18 hours. Hoechst staining, high content cell imaging and RT-PCR were used to detect the apoptosis of hippocampal neurons and the expressions of apoptosis-related ETS-like 1 transcription factor(ELK-1), C-Jun N-terminal kinase(JNK) and c-Fos proteins and genes.

Results: Compared with the blank group, the apoptotic number of hippocampal neurons in the model group was increased significantly, and the expression levels of ELK-1, JNK and c-Fos were increased significantly (P<0.05). Compared with the model group, the local bright spots of hippocampal neurons in the Zuogui Jiangtang Jieyu recipe-containing serum group and the positive drug-containing serum group were decreased significantly, and the number of apoptotic cells was decreased significantly. The expressions of JNK, c-fos protein and mRNA were down-regulated significantly (P< 0.05), and the neural network and dendritic junction were improved significantly.

Conclusion: Zuo Gui Jiang Tang Jie Yu Formula can reverse the expressions of ELK-1, JNK and c-Fos signals in hippocampal neurons under DD environment and play an anti-apoptotic effect.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Depression* / drug therapy
  • Diabetes Complications* / drug therapy
  • Diabetes Mellitus*
  • Drugs, Chinese Herbal* / pharmacology
  • Hippocampus* / drug effects
  • MAP Kinase Kinase 4 / drug effects
  • Neurons
  • Proto-Oncogene Proteins c-fos / drug effects
  • Random Allocation
  • Rats
  • ets-Domain Protein Elk-1 / drug effects

Substances

  • Drugs, Chinese Herbal
  • Elk1 protein, rat
  • Proto-Oncogene Proteins c-fos
  • ets-Domain Protein Elk-1
  • zuogui
  • MAP Kinase Kinase 4