| Background Hypertrophic scar(HS)is the common results from an excessive wound-healing response to refractory skin injury or other inflammation.Hyperplastic scar will cause local skin redness,swelling,pain and itching,and severe scar hyperplasia will lead to limited joint movement,which not only affect the appearance,but also has a huge impact on the daily life of patients.Currently,various methods are used to treat hypertrophic scar clinically,but they are usually accompanied by certain side effects or poor efficacy.Therefore,it is still an urgent problem to find new methods or drugs for scar treatment.Botulinum toxin is the bacterial endotoxin secreted by botulinum toxin.Botulinum toxin type A(BTXA)is the most widely used toxin.Originally used to treat blepharospasm and strabismus,BTXA was accidentally discovered in the course of treatment to improve eyebrow wrinkles and then used in cosmetic surgery.BTXA inhibits the release and retention of acetylcholine,thereby blocking neuromuscular transmission and movement.This function is also used in many clinical disciplines,such as neurology,urology,etc.In recent years,studies have found that BTXA can alleviate hypertrophic scar and improve the appearance and hardness of scar,but the specific mechanism of its effect is still unclear.With the development of gene research and technology,scholars have found that many mi RNAs play a role in hypertrophic scar,especially the expression of micro RNA(mi R)-21 is closely related to hypertrophic scar.Therefore,the purpose of this study was to explore whether the expression level of mi R-21 in the treatment of hypertrophic scar by BTXA had changed,so as to find new targets for the treatment of hypertrophic scar.Objective(1)In vivo and vitro experiments,after treating hypertrophic scar tissues and cells with different doses of BTXA.(2)Scar related fibrosis indicators were detected and mir-21 expression levels in scar tissues and fibroblasts were simultaneously detected to explore the possible effect of mir-21 on inhibiting scar formation.Methods(1)Hypertrophic scars isolated from the ears of New Zealand big-eared rabbits and treated with different concentrations BTXA in vivo experiment.Fibroblasts were harvested from tissue specimens of human hypertrophic scars.(2)The cells proliferation and activation with different dosages BTXA was analyzed by MTT,expression of fifibrosis markers such as COL1 and ?-SMA in scar tissue and fibroblast by Western blot,COL-I,?-SMA and mi R-21 expression level in each group was detected by the method of Q-PCR.Results(1)In animal experiments,the fibrosis index and scar index after BTXA treatment were significantly lower than those in the untreated group,and with the increase of BTXA concentration,the fibrosis index and scar index in the high concentration group were lower than those in the low concentration group(P < 0.05).(2)In vitro,the fibroblast related fibrosis index after BTXA treatment was lower than that in the untreated group,and was correlated with the concentration.The fibrosis inhibition effect of high concentration of BTXA was higher than that in the low concentration group(P < 0.05).Western blot results of both animal experiment and vitro experiment showed that the expression levels of COL1 and ?-SMA decreased with the increase of BTXA dose,and Q-PCR results revealed that BTXA inhibited the activation and proliferation of fibroblasts in a concentration dependent manner and decreased in parallel the expression of mi R-21,COL1 and ?-SMA(P < 0.01).Conclusions(1)BTXA can reduce collagen deposition and fibroblast proliferation in scars,thus effectively relieving the formation of hypertrophic scars.(2)By detecting the expression level of mir-21 in scar tissue and fibroblasts,These results indicated that treatment with different doses of BTXA might be concentration dependent for inhibiting hypertrophic scars and provide a novel anti-fibrotic mechanism,which might be associated with its ability to repress the expression of mi R-21. |
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