The Effect Of Tamoxifen On Fibroblast Proliferation And Epidural Scar Adhesion

Objective:To investigate the effect of TAM on fibroblast proliferation and epidural scar adhesion.Methods:Twenty-four male Wistar rats(weighing 250-270 g)were randomly divided into four groups.The rats were anesthetized by pentobarbital sodium through intraperitoneal injection,and the L1 vertebral plate was removed.The rats were gavaged with different concentrations of TAM every day for 1 month after laminectomy and then sacrificed with a fetal dose of pentobarbital sodium.The rats were intracardially perfused with 4%paraformaldehyde.The entire L1 centrum was removed and immersed with 4%paraformaldehyde.The specimens were embedded in paraffin after decalcification using ethylenediamine tetraacetic acid(EDTA).Successive sections were obtained through the L1 vertebra.Histological and immunohistochemical analysis were used to evaluate the effects of TAM on preventing epidural scar adhesion.Fibroblasts were cultured and treated with different concentrations of TAM and the same concentration for different times.Cell Counting Kit-8(CCK-8)detection,cell cycle analysis and western blot analysis were used to detect the roles of TAM in regulating fibroblast proliferation.Results:Histological analysis showed that TAM could reduce epidural scar adhesion.Immunohistochemical analysis showed that the phosphorylation level of ATK in epidural scar tissue was decreased after TAM treatment.CCK-8 detection showed that TAM could inhibit fibroblast viability,cell cycle analysis showed TAM could inhibit fibroblast proliferation and arrest cell in G1 phase,western blot analysis showed that TAM could decrease the phosphorylation level of AKT and the expression of cyclinD1 and increase the expression of P21 and P27.The results demonstrated that TAM could inhibit fibroblast proliferation and prevent epidural scar adhesion.Conclusion:Tamoxifen inhibits fibroblast proliferation and prevents epidural scar adhesion by regulating the AKT phosphorylation level and its downstream gene expression.