| Failed Lumbar Surgery Syndrome(FBSS)is a serious complication after laminectomy,which is manifested in the recurrence of intractable or unexplained pain after surgery,and even affects the sensory and motor functions of the lower limbs.Excessive epidural fibrosis makes the lumbar spinal canal stenosis,direct or indirect compression or restriction of nerve roots,which is one of the main reasons for FBSS after laminectomy.The appearance of excessive epidural fibrosis after surgery often means the spine Failure of the plate resection surgery.Drugs and conservative treatments have limited relieving effects on this type of nerve compression pain,and there is no long-term efficacy observation.The second or third surgical treatment is also limited to the original excessively fibrotic epidural tissue,which has a high surgical failure rate.Therefore,for laminectomy,the main focus is to prevent excessive fibrosis of the epidural tissue.During the first laminectomy,how to effectively and safely reduce epidural fibrosis to prevent surgical failure is of great significance.Pirfenidone(PFD)is a new type of oral pyridone derivative that can inhibit the formation of collagen.It has been widely studied for the treatment of idiopathic pulmonary fibrosis.It has shown anti-fibrosis in vivo and in vitro Activity,and shows similar activity in a variety of animals.At present,there is no obvious research showing that PFD can be used as the treatment of epidural fibrosis.Pirfenidone may have broad application prospects for the prevention of excessive epidural fibrosis after laminectomy.Objective: This present study aims to assess the effect of pirfenidone(PFD)on reducing laminectomy-induced epidural fibrosis in vivo and inhibiting fibroblast proliferation,migration or adhesion in vitro.Methods:(1)In animal experiments,first fifty healthy male Sprague-Dawley rats were randomly divided into five groups,fake surgery group,control group(0 mg/ml),low PFD concentration group(1 mg/ml),medium PFD Concentration group(5 mg/ml)and high PFD concentration group(10 mg/ml).Except for the sham operation group,all rats were subjected to laminectomy and then treated with cotton block immersing with corresponding concentrations of PFD.After 4 weeks,all L1 vertebrae of each rat were removed.Finally,the degree of epidural fibrosis was evaluated by histological analysis.(2)In vitro experiments,the effect of PFD on proliferation inhibition was evaluated with flow cytometry,CCK-8,Ed U and Western-blotting assays.Altered properties in migration and adhesion were confirmed by wound-scratch,transwell,immunofluorescence(IF),cell adhesion and Western-blotting assays.The PI3 K gene was overexpressed through the construction of lentiviral expression vector.The obtained PI3 K gene overexpression fibroblasts and PFD drug intervention were used to verify the possible pathway on PFD intervention.Results:(1)In vivo,an obvious reduction in epidural fibrosis was observed in groups topically treated with PFD.(2)In vitro,the results of flow cytometry,CCK-8,Ed U and Western-blotting assays showed that PFD reduced fibroblast proliferation by a dose-dependent manner.The results of wound-scratch,transwell,IF,cell adhesion and Western-blotting assays showed that the migration and adhesion of fibroblasts could be inhibited and the cytoskeleton could also be altered in a dose-dependent manner.(3)The inhibitory effect of PFD could be partially reversed in the PI3 K overexpression experiment,which indicated that the capability of PFD to inhibit fibroblast proliferation,migration and adhesion might be through the PI3K/AKT signaling pathway.Conclusions:(1)Topical application of PFD significantly inhibited the epidural fibrosis after laminectomy in rats in vivo.(2)PFD inhibits fibroblast proliferation,migration and adhesion in vitro.And the inhibition of PFD on fibroblast proliferation,migration and adhesion of fibroblasts may be through the inhibition of PI3K/AKT signaling pathway. |
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