| BackgroundScar is a common complication in the healing process after burn trauma and surgical treatment.Its essence is a kind of skin fiber proliferative diseases,which is due to excessive healing,leading to abnormal fibroblasts proliferation and excessive deposition of extracellular matrix.Median sternotomy is the most prone to the formation of hypertrophic scar in linear surgical incision.As is reported,the incidence of median sternotomy hypertrophic scar or keloid is more than 50 percent in the Asian population,and the scar accompanied by pain and local itching often makes the patients seek help from dermatologist or orthopaedist.Botulinum toxin type A(BTA)is a neurotoxin produced by Clostridium botulinum in the process of breeding.It is held together by a heavy chain and a light chain with the disulfide bond.Now studies have showed that BTA has effects on prevention and treatment of hypertrophic scar,but most of those are retrospective clinical study,and little is known about the underlying mechanisms of action.PurposesThe aim of the study is to design a prospective,randomized,placebo-controlled trial to elucidate the effect of BTA in the prevention and treatment of median sternotomy scar,and to explore its mechanism of prevention and treatment of scar by in vitro culturing hypertrophic scar-derived human fibroblasts(HSFs).We hope that the early intervention with BTA will significantly decrease or reduce the postoperative scar,expecting to achieve breakthrough in the field of scar prevention and provide new scientific reference for the prevention and treatment of postoperative scar.Methods1.A single-center,prospective,randomized controlled trial was conducted to evaluate the efficacy of BTA injected in the early postoperative of median sternotomy for the purpose of preventing scar formation.All the entire median sternotomy wounds were divided into the upper half and the lower half by the paired design.Both halves of the wound were randomized to receive treatment with either BTA or normal saline.At six months follow-up,scars were assessed using the Vancouver Scar Scale(VSS),the scar widths were measured and patients were asked to evaluate their overall satisfaction.2.To explore the mechanism of BTA on prevention and treatment of scar,we cultured HSFs and observed the effect of BTA on TGF-?1 induced collagen and ?-SMA expression.HSFs were divided into four groups,blank control,TGF-?1,TGF-?1+2u/ml BTA,TGF-?1 + 4u/ml BTA.The total amount of collagen was examined by Sirius red staining.Enzyme linked immunosorbent assay was used to detect the amount of collagen?and collagen ? in the supernatant.Western blot was used to detect the protein expression of collagen ?,collagen ? and ?-SMA.The real-time quantitative PCR was used to detect the m RNA expression of collagen ?,collagen ? and ?-SMA.Results1.17 patients with median sternotomy wound completed the entire study.At six months follow-up,the mean VSS score for the BTA-treated group was 3.44 ± 1.68 and the normal saline control group was 6.29 ± 2.39,there was statistically difference between the two groups(P<0.05).The scar width of BTA-treated group was 2.73 ± 1.44 mm and normal saline control group was 5.23±2.75 mm,there was statistically difference between the two groups(P<0.05).The patient satisfaction score for the BTA-treated group was 1.41 ± 0.62 and the normal saline control group was 2.71±0.85,there was statistically difference between the two groups(P<0.05).2.BTA(2u/ml or 4u/ml)reduced the TGF-?1 induced collagen production in the HSFs and had a strong antagonistic effect on the protein and m RNA level of collagen?,collagen ? and ?-SMA induced by TGF-?1.Besides,it suppressed the secretion of collagen ? and collagen ? in the supernatant.The effect of BTA was dose-dependent within a certain range.Conclusion1.BTA injecting in the early postoperative can decrease the scar formation and reduce the scar width in median sternotomy wound,and the overall appearance is more satisfactory.2.BTA can reduce the expression of collagen induced by TGF-?1 and inhibit the differentiation of fibroblast to myofibroblast and decrease collagen synthesis.3.This study demonstrates that prevention and treatment scar by BTA injection,with simple manipulation,is safe and effective,and it also provides a new way for the early prevention and treatment of postoperative scar. |
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