Abstract:
OBJECTIVE To explore the mechanism by which 717 Jiedu Decoction promotes the repair of local damaged tissue in rats bitten by Agkistrodon halys through regulating the VEGF/ERK signaling pathway.
METHODS Sixty SPF-grade healthy SD rats were selected and randomly divided into the normal control group(control group), the Agkistrodon halys bite model group(model group), the anti-Agkistrodon halys venom serum group(serum group), and the high-, medium-, and low-dose group of 717 Jiedu Decoction(717-H group, 717-M group, 717-L group). Histopathological changes in the gastrocnemius muscle were observed using hematoxylin-eosin(HE) and Masson staining. Immunohistochemistry was used to detect the expression of cytokine-induced neutrophil chemoattractant-1(CINC-1) and intercellular adhesion molecule-1(ICAM-1). The levels of vascular endothelial growth factor(VEGF), nerve growth factor(NGF), extracellular signal-regulated kinase(ERK), and interferon-γ(IFN-γ) in serum were measured by enzyme-linked immunosorbent assay (ELISA). The protein and mRNA expression levels of VEGF, ERK, NGF, and IFN-γ in wound tissue were detected by Western blotting and reverse transcription-quantitative polymerase chain reaction(RT-qPCR), respectively. Reactive oxygen species (ROS) levels were measured using a biochemical assay kit.
RESULTS The model group showed marked tissue damage, while the serum group and each dose groups of 717 Jiedu Decoction exhibited varying degrees of improvement, with the 717-H group closely resembling the control group. The model group also showed increased collagen deposition and ROS levels, which were significantly reduced by anti-Agkistrodon halys venom serum and 717 Jiedu Decoction. CINC-1 and ICAM-1 expression was significantly upregulated in the model group, whereas their expression was downregulated by anti-Agkistrodon halys venom serum and 717 Jiedu Decoction. VEGF, NGF, ERK, and IFN-γ were upregulated in the model group, and both serum group and 717-H group showed strong inhibitory effects on these factors.
CONCLUSION 717 Jiedu Decoction effectively reduces tissue fibrosis, oxidative stress, and inflammatory responses. Its mechanism may be related to its inhibition of the VEGF/ERK signaling pathway. The research provides a new target for the prevention and treatment of local tissue damage induced by Agkistrodon halys venom.