| failed back surgery syndrome(FBSS)is defined as a syndrome in which patients are still experiencing recurrent and/or persistent lower lumbar pain,with/without radiation neuropathic pain after lumbar surgery.The global incidence of FBSS was reported to be from 10 to 40%.FBSS can be led by a variety of factors.During the perioperative period,the factors can be categorized as preoperative,intraoperative and postoperative factors.Preoperative factors consist of:1.the psychological and social factors of patients;2.the surgical related factors;3.diagnosis missing.Intraoperative factors mainly included:1.poor surgical skills;2.wrong segment choice;3.excessive decompression.Postoperative factors mainly included:1.intervertebral disc herniation;2.intervertebral space infection;3.epidural adhesion(EA).Laminectomy is surgical operation in epidural lacunae.After laminectomy,it is difficult to avoid the production of epidural scar tissue during the postoperative healing process.Excessive epidural scar tissue with the formation of epidural fibrosis(EF),can lead to the nerve root extrusion/tethered,while interfering with cerebrospinal fluid flow,eventually leading to the cccurrence and deterioration postoperative symptoms.EA has become one of the important causes of FBSS.It is widely accepted that the optimal treatment for EA is to prevent its formation.The majority of domestic and foreign scholars have performed many researches to prevent the formation of EA in both clinical and basic researches.Recently,some scholars have made extensive attempts to prevent EA through animal models.Including nonsteroidal anti-inflammatory drugs,immunosuppressive agents,calcium channel blockers,stem cells transplantation,autologous fat transplantation,bone cement grafting,drug gel applications,honey etc,have been demonstrated to a certain extent to prevent EA formation.But so far,there has been no efficient method to be widely used in clinical practice.Salvianolic acid B(Sal B),the rhizome extract of Salvia miltiorrhiza,is one of the main water-soluble components of Salvia miltiorrhiza,and the main constituent of Salvia miltiorrhiza.Recently,Sal B has been used in the fields of anti-fibrosis,anti-oxidation,anti-tumor,anti-inflammatory,and inhibition of apoptosis.Some researchers have reported Sal B's roles in the inhibition of liver fibrosis,entailing the progress of pulmonary fibrosis,prevention and treatment of diabetic nephropathy,tumor killer,inhibition of cerebral ischemia after ischemia and reperfusion,and the treatment of neurodegenerative diseases.Based on the above researches,the objectives of the present study were to explore the safety,efficacy and feasibility of Sal B in preventing epidural adhesion after laminectomy in rats,and to explore its mechanism.The overall study is divided into two parts:Part I,the effect study of salvianolic acid B on the prevention epidural adhesion after laminectomy in rats.In this section,60 Wistar rats were randomly divided into three groups:Sal B group,Vehicle treatment group,and control group,with 20 rats in each group.Sal B was dissolved in normal saline solution to prepare Sal B saline solution(7.5 mg/ml).The animals were weighed by electronic scale,and were injected with chloral hydrate for intraperitoneal anesthesia according to animal weight(0.3ml/100g).Rats were numbered after satisfactory anesthesia.The rats were operatered according to the classic lumbar laminectomy procedure:skin in L1,L2 level was treated with iodophor disinfection for 3 times.Placed in prone position,rats were with a median incision about 4-5cm.Skin layer and the superficial fascia were split and L1-L2 lumbar paraspinal muscles were blunt dissected to expose L1-L2 spinous process.A standard laminectomy was performed on L1-L2 section and the dura was clearly exposed.The bone was about 4mm X 5mm.Following washing with saline,the wound closure was conducted.After the critical phase in perioperative period intragastric administration was performed:rats in Sal B group received salvianolic acid B solution with dosage of 30mg/kg/d,Vehicle group were given normal saline treatment,control group received no treatment.All rats were fed separately with the maintaining room temperature between 20-28 degrees.The postoperative injection of antibiotics was performed for 3 days.The wound was closely observed to avoid infection.Four weeks after surgery,5 rats from each group were randomly selected to be tested with Rydell score.The selected rats were killed by overdose anesthesia.The scar tissues were harvested,dried,and cryopreservated.The hydroxyproline in the epidural scar tissue was detected.Masson trichrome staining,hematoxylin eosin staining,VEGF immunohistochemical staining were conducted.The expression of inflammatory factors in the epidural scar tissues were determined by Real-time PCR.SPSS software was used to analyze the results.ANOVA and q test were used to compare the differences between groups.P<0.05 was considered statistical different.The recovery of all rats was uneventful.In the laminectomy sites treated with Sal B,the dura mater showed less adhesion.Collagen deposition was significantly lower in the Sal B group than the other two groups.In addition,both fibroblast and inflammatory cell counting in the laminectomy sites treated with Sal B showed better grades than those in the other two groups.The expression of VEGF and inflammatory factors in operative sites also suggested better results in the Sal B group than the other two groups.Sal B inhibits fibroblast proliferation,blood vessel regeneration,and inflammatory factor expression.Thus,Sal B is able to prevent epidural scar adhesion in post-laminectomy rats.Part ?,the mechanism study of salvianolic acid B on the prevention epidural adhesion after laminectomy in rats.Forty healthy adult male Wistar rats were divided into four groups(n=10 per group):1)10 mg/kg Sal B;2)30 mg/kg Sal B;3)50 mg/kg Sal B;4)Saline(vehicle treatment,control group).All animals underwent a laminectomy at the lumbar 1-2(L1-2)level.After intragastric treatment,all rats were sacrificed at post-operative week 8.The extent of the epidural scar,the regeneration of the vasculature and the expression levels of vascular endothelial growth factor(VEGF)were analyzed.The animals' recovery was uneventful during the experimental period.The extent of the epidural scar,the regeneration of the vasculature and the expression levels of VEGF suggested better outcomes in the Sal B treated groups.Sal B exerted the ability to prevent the formation of an epidural scar and vascularization at the laminectomy sites.The effects of Sal B were dose-dependent,with the 50 mg/kg Sal B group showing the best outcomes compared with the other groups.Post-operative intragastric application of Sal B can prevent the formation of epidural scarring.Sal B exerted these effects in a dose-dependent manner,and 50 mg/kg was shown to have the best efficacy in the present study.The results of this study reveal that Sal B could be a potential therapy for EF and valuable for further research.Following conclusions were obtained from our study:(1)Sal B has a significant effect in the prevention of epidural adhesion formation after laminectomy;(2)Sal B showed dose-dependent effect in the prevention of epidural adhesions after laminectomy.The results suggested 50mg/kg of Sal B had the best efficacy;(3)Sal B can inhibit the process of collagen deposition,inflammatory reaction,fibroblast proliferation and vascular regeneration after laminectomy.This study provided a new method for clinical prevention of epidural adhesion.The present study demonstrated the anti-fibrosis role of Sal B on preventing epidural adhesion.Meanwhile,compared with 10mg/kg and 30mg/kg,50mg/kg was suggested to be optimal concentration. |
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