A Preliminary Study On Combined Use Of Penicillin,Amikacin And Budesonide To Prevent Tracheal Stenosis In Rabbits

Objective To study the expression of histone deacetylase 2(HDAC2)in the rabbit tracheal stenosis models,and its role in the development of tracheal stenosis,and explore the effect of combined use of penicillin,amikacin and budesonide in the treatment of rabbit tracheal stenosis and its possible mechanisms to find new methods for the treatment of benign tracheal stenosis.Methods Sixty rabbits were randomly divided into ten groups,and six rabbits in each group,namely group K:blank control group,group S:model group,group H:small-dose erythromycin group,group Q:penicillin group,group A:amikacin group,group B:budesonide group,group HB:erythromycin plus budesonide group,group QB:penicillin plus budesonide,group AB:amikacin plus budesonide,group QAB:penicillin amikacin plus budesonide.Group K wasn't received any treatment,the other groups of rabbits were tracheotomy and brushed back and forth with nylon brush 20 times to damage the tracheal wall to produce benign tracheal stenosis animal models,7 days before surgery to 9 days after surgery,group S was given physiological saline irrigation stomach,group H was given a small dose of erythromycin 15mg/kg/d gavage,group Q was given penicillin 40,000U/kg/d intramuscularly,group A was given amikacin 10mg/kg/datomization,group B given budesonide 50ug/kg/d atomization.Group HB,group QB,group AB,and group QAB were jointly appealed several drug doses and administration methods.On the 10 th day after operation,rabbits in each group were sacrificed and the narrow section of the trachea was separated to measure the degree of tracheal stenosis.RNA and protein were extracted from the granulation tissue in the stenosis and the relative expression of HDAC2 mRNA,IL6 mRNA and IL8 mRNA in the granulation tissue were detected by real-time fluorescence quantitative PCR.The relative expression of HDAC2 protein was detected by western blotting.Results(1)The tracheal stenosis of group S was significantly higher than that of the control group K.Compared with group S,the degree of trachea stenosis was reduced in group H,group Q,group A,group B,group HB,group QB,group AB and group QAB,and all the reductions were statistically significant(P<0.05).The group H,group Q,group A,and group B were compared with the model group S respectively,and the degree of tracheal stenosis was the lowest in the group Q,the differences were statistically significant(P<0.05).Group H compared with group HB,group Q compared with group QB,the same as group A and group AB,the differences were statistically significant(P<0.05).Compared with each combination group,the degree of tracheal stenosis was the lowest in the group QAB,and the differences were statistically significant(P<0.05).(2)Compared with group K,the expression of HDAC2 mRNA and HDAC2 protein were decreased in model group S.Compared with group S,the expression of HDAC2 mRNA and HDAC2 protein were up-regulated in group H,group Q,group A,group B,group HB,group QB,group AB and group QAB,and group QAB had the most significant up-regulation,the differences were statistically significant(P<0.05).(3)Theexpression of IL6 mRNA and IL8 mRNA in the group S were significantly higher than that in the group K.Compared with group S,the expression of IL6 mRNA and IL8 mRNA were down-regulated in group H,group Q,group A,group B,group HB,group QB,group AB and group QAB,and the group QAB had the most significant down-regulation,and the differences were statistically significant(P<0.05).(4)The Pearson correlation coefficient of tracheal stenosis and relative expression of HDAC2 mRNA was r=-0.96,P<0.05.The degree of tracheal stenosis is highly negatively correlated with HDAC2,in other words the greater the degree of tracheal stenosis,the lower the relative expression of HDAC2.Conclusions(1)The persistence of airway inflammation was an important cause of stenosis after tracheal injury.(2)The expression of HDAC2 in acute inflammatory phase of rabbits tracheal stenosis after their tracheal injury was down-regulated,resulting in local inflammatory reaction imbalance and promoting the occurrence and development of tracheal stenosis.(3)Up-regulation of HDAC2 could reduce the intensity of acute inflammatory responses in the rabbits tracheal stenosis,thereby reducing the degree of tracheal stenosis.(4)The combined use of penicillin,amikacin and budesonide could prevent and treat tracheal stenosis after tracheal injury in rabbits through anti-inflammatory,anti-infection,and up-regulating the expression of HDAC2.