Temporal and spatial expression of Phosphodiesterase-4B after sciatic nerve compression in rats and its mechanism of action on sciatic nerve repair

Abstract

Background

Macrophage phenotype transformation is vital in sciatic nerve injury. The study of biomolecule expression and its impact on macrophage phenotype transformation is a current research focus.

Material and methods

We created a rat model of sciatic nerve compression injury to examine the expression of PDE4B and the distribution of M1 and M2 macrophages over time and their relationship. We confirmed the effect of inhibiting PDE4B expression on macrophage phenotype changes and its role in sciatic nerve injury repair. The experiments consisted of immunofluorescence, western blotting, HE staining, TEM, and behavioral evaluation. Investigate in vivo experiment results with RAW264.7 cells in vitro. PDE4B knockdown lentivirus was transfected into RAW264.7 cells and stimulated with LPS and IFN-γ. We assessed CD86 and CD206 expression using flow cytometry and western blot. The relationship between PDE4B and the TLR4/NF-κB pathway was studied.

Results

PDE4B peaked on day 7 after surgery, alongside the highest M1 macrophages count. PDE4B and M1 macrophages decreased, and M2 macrophages increased. PDE4B inhibition reduced M1 macrophages, increased M2 macrophages, suppressed inflammation, and promoted sciatic nerve repair while alleviating pain. In vitro experiments confirmed that PDE4B regulated macrophage phenotype via the TLR4/NF-κB pathway. Inhibiting PDE4B disrupted this pathway and promoted M2 macrophage transformation.

Conclusions

In the sciatic nerve injury, PDE4B expression is linked to the M1 macrophage phenotype. Low PDE4B expression facilitates the M1 to M2 macrophage transformation and supports sciatic nerve repair. The TLR4/NF-κB pathway is involved in this process.