The Effect Of Resveratrol On Prevention Of Surgery-induced Epidural Fibrosis In Laminectomy Rats

In recent years, along with the technical progress of spinal operation, CT、MRI and other imaging diagnostic level improved, and the requirements of people on the high quality of life, the number of patients with lumbar decompression operation are growing.With the development of the lumbar spine operation, failed back surgery syndrome (FBSS) occurs widely. Its incidence is as high as5%-40%and seriously affects the effect of operation treatment.The main symptoms of lumbar laminectomy are chronic nerve root pain or lumbar leg pain, weakness, numbness. The cause of failed back surgery syndrome varied and complex, but many researchers think the epidural fibrous scar tissue adhesion after lumbar laminectomy is one of the important reasons. The mechanism is:after laminectomy, operation trauma and local inflammatory reaction, and the formation of hematoma, the inflammatory cytokines mediated, fibroblast proliferation, collagen synthesis increased, in the epidural operation area of fibrous scar formation, epidural fibrosis (EF) happens. Fibrous scar tissue retract, extrust the dura, nerve root, and the influence of blood supply, so result in low back pain symptoms in clinic.The medical professer recognized that reoperation treatment of FBSS was unbenefit [134]. We carefully selected a group of FBSS patients and FBSS was confirmed by the epidural scar adhesion. In8cases, the excellent and good rate was only50%operation, results were not very satisfactory.Epidural fibrosis after lumbar laminectomy may be the underlying cause for the cases of failed back syndrome. Various materials and agents have been employed to prevent epidural fibrosis, but only moderate success has been reached.Resveratrol (3,5,4’-o-trihydroxystilbene), which is found in grapes,-red wine, various other fruits and medicinal plants, has exerted its variety of biological properties including anti-carcinogenic, anti-oxidant and anti-inflammatory in a number of previous literatures. Also, it can cause vasodilatation and inhibit platelet aggregation. A group of studies have reported that resveratrol is able to prevent the postoperative scar adhesions in animals. After an extensive review, this is the first study on the effect of resveratrol on prevention EF.The object of this study was to investigate the effects of resveratrol on the prevention of post-laminectomy EF formation in laminectomy rats. This topic used animal experiment and established the model of the rat lumbar vertebrae plate resection.the aims were that resveratrol can inhibit the hyperplasia of fibrous tissue, prevent scar tissue adhesion after lumbar operation and explore the effects of resveratrol in inhibiting epidural fibrosis.The text provided the experimental basis and solution for the mechanism of the occurrence of FBSS.Part I Clinical observation on the reoperation treatment of FBSS induced by the epidural scar adhesionObjective To observe the clinical effect of the reoperation treatment of FBSS induced by the epidural scar adhesionMethods1.60cases of FBSS were carried out in accordance with the preestablished conditions from2005-2012,8patients met the study criteria were reoperated.2.A1l8patients carried out comprehensive imaging examinations, including X-ray, CT, MRI.Patients were conducted psychological testing in accordance with the MMPI standard before operation.Operation plan was made carefully after detailed preoperative discussion.3. Operations were performed under general anesthesia. Curette scrap the scar tissue. The movement was careful and gentle and achieved a good haemostasis. To observe the hyperplasia and adhesions of the scar tissue and HE staining. 4. The judgment standard of curative effect after operation used Macnab and operation effect was evaluated.Results1. There were significantly different in time of operation, the bleeding volume and average days of hospitalization between operation and reoperation, it had statistical significance (P<0.05).2. A large number of dense fibrous scar tissue were observed during operation,and worked closely with the epidural bursa and the nerve root. In HE staining, lots of the fibrous tissue hyperplasia and the dense fibrous tissue were observed.3. All patients were followed up from12months to36months. The effect of operation treatment again was evaluated in accordance with the Macnab and the excellent and good rate was50%.Conclusion1. Compared with the first operation,the reoperation increased significantly in time of operation, amount of bleeding during the operation and average length of stay.2. Operation skill was high and difficult. Stripping scar tissue was very hard.There was great influence to the nerve roots and dural.3. Once again the operation treatment of FBSS results were not very satisfactory. there will has bright prospects than operation treatment if we take some measures for prevention of epidural scar adhesion after lumbar spinal canal decompression. Part Ⅱ The effect of resveratrol on prevention of surgery-induced epidural fibrosis in laminectomy ratsObjective To investigate the mechanism of resveratrol on prevention of epidural fibrosis and provided the experimental basis and solution for the mechanism of the occurrence of FBSS.Methods1.A controlled double-blinded study was performed in60healthy adult Sprague-Dawley rats that underwent lumbar laminectomy at the L1-L2levels. They were divided randomly into3groups (1,2and3) of20rats each. Group1:resveratrol treatment group; Group2:resveratrol dilution saline treatment group; Group3:Sham group (rats underwent laminectomy without treatment).2.Preparation of animal model:operator followed the experimental model of standard operation in sterile conditions. Each rat was marked independent number in the tail. Operator started the operation doing a dorsal midline incision,cut skin and superficial fascia layer by layer. Using1mm micro bone biting forceps to remove spinous process and lamina of vertebra, made bone window about4mm×5mm and exposed the dura mater.3.All rats were killed4weeks post-operation. The Rydell score, hydroxyproline content, vimentin cells density, fibroblasts density and inflammatory factors expressional levels were conducted to evaluate the effect of resveratrol.Results1.The laminectomy was well tolerated by all rats without wound infection, neurological deficit and cerebrospinal leak. In the resveratrol group, macroscopic observation showed that soft or weak fibrous adhesion was observed in the laminectomy sites. However, in the laminectomy sites of rats treated with saline or nothing, severe epidural scar adhesions were seen. And it was difficult to dissect the scar adhesions accompanied with bleeding and disruption of the dura mater.2.HPC concentration in epidural scar tissue:The resveratrol group (31.32±4.72μg/mg) showed a significantly reduction compared with that of the saline group (48.92±3.54μg/mg, P<0.01) and sham group (54.17±4.39μg/mg, P<0.01). The content in saline group showed no significant difference compared with that of sham group (P>0.05). In the laminectomy sites of the saline group and sham group, dense epidural scar tissue with widespread adhesions to dura mater and dorsal muscle were observed. However, in the laminectomy sites of the resveratrol group, loose or little scar adhesion was seen.3. For the Immunohistochemistry analysis of vimentin cells in epidural scar tissues: Less positive vimentins in the resveratrol group was less than those of other2groups. The density of positive vimentins in the saline group was similar with that of sham group.4.The results of mRNA expressional levels of both TGF-(31and IL-6showed that the resveratrol group was lower than those of the saline group (P<0.01) and sham group (P<0.01); the expressions between saline group and sham group were not significantly different (P>0.05).Conclusion1、Resveratrol solution could inhibit the proliferation of fibroblast,the activity of prolyl hydroxylase. The original collagen fiber synthesis is unable to secrete, it reduced collagen synthesis. Resveratrol solution could inhibit the synthesis of inflammatory factor, effect anti-fibrosis, anti-scar, anti-collagen deposition, and anti-inflammatory.2、The mechanism of the resveratrol was realized by expression of lower the level of inflammatory factor IL-6and TGF-β1and reduced hydroxyproline deposition, its effect is satisfactory.3、It evaluated the degree of the scar tissue on the basis of the the content of hydroxyproline,and improved the accuracy of the experiment.