A Preliminary Study Of Trauma,IL-8,MMP-9 And NCAM-1 In Benign Tracheal Stenosis Of Rabbits

Part 1 To study the role of the damage of tracheal wall in the formation of rabbit airway stenosisBackground and Objective:Benign airway stenosis refers to the airway stenosis caused by various non-malignant tumor lesions,which pathogeny is complex,including tuberculosis,benign tumors of airway,tracheobronchomalacia,tracheal intubation or tracheotomy.In recent years,more and more hospitals apply invasive mechanical ventilation for treatment severe patients,then the incidence of long-term tracheal intubation or tracheotomy complicated with airway stenosis has gradually increased,accounting for about 61.4%.Airway stenosis caused by tracheotomy may lead to different degrees of dyspnea,weaning,difficult extubation,and even life-threatening.However,at present,the mechanism of tracheotomy complicated with airway stenosis is still unclear,and prevention and treatment of that are difficulty,so it is worth further exploring its pathogenesis.In recent years,scholars at home and abroad established animal model of benign airway successfully by mechanical damage,thermal ablation damage,chemical damage,endotracheal intubation,partial cartilage ring excision.Trauma is the important reason for the airway stenosis after intubation,but the extent of damage of tracheal wall in the formation of airway stenosis needs to be further explored.In this study,we adopt different methods to damage the tracheal wall of rabbits,and to study the effects of different degrees of damage to the tracheal wall on the airway stenosis after intubation.Methods:Four methods were adopted to damage tracheal wall of rabbits.The group A showed tracheal mucosa damaged slightly(the tracheal mucosa was damaged by the nylon brush under the bronchoscope)?the group B showed tracheal mucosa damaged severe(incise the cartilage tracheal and then closed after scraping of tracheal mucosa with a nylon brush),the group C showed destruction of tracheal cartilage(tracheotomy combined with damage cartilage by vascular clamp),the group D showed destruction of tracheal cartilage and mucosal injury(incise the cartilage trachea,damage cartilage by vascular clamp and scraping of tracheal mucosa with a nylon brush).At 1,2,3 and 4 weeks after surgery,7 experimental rabbits in 4 groups were examined by tracheoscopy to observe the stenosis type and stenosis rate.At 4 weeks,we used chest MSCT scanning measure the degree of stenosis.The formation of airway stenosis was confirmed by anatomical and pathological results,the rate and type of tracheal stenosis were compared.Differences were considered statistically significant at P<0.05.Results:(1)The successful rate of tracheal stenosis at 4 weeks:The success rate of four groups was 57.14%(16/28).No stenosis was observed in the group A,the group of B was 28.57%(2/7),the group of C was 100%(7/7),the group of D was 100%(7/7).The successful rate of tracheal stenosis of the group of C and D were higher of the group of A and B,there was a significant difference of the successful rate of tracheal stenosis in four weeks after the operation(P<0.05).The successful rate of tracheal stenosis of the group of B was higher of the group of A,there was no significant difference of the successful rate of tracheal stenosis between the group A and the group B(P>0.05).There was no significant difference of the successful rate of tracheal stenosis between the group C and the group D(P>0.05).(2)Stenosis types at different time periods and different injury methods under tracheoscopy:the successful rate of tracheal stenosis in the group A at 1,2,3 and 4 weeks after surgery was 0%(0/7).In group B,the rate of granulation hyperplasia at 1,2 and 3 weeks after surgery was 28.6%(2/7),the rate of granulation hyperplasia was 14.3%(1/7)at 4 weeks after surgery,the rate of scar stricture was 14.3%(1/7).There are 14 rabbits of the group C and D,the rate of granulation hyperplasia at 1,2 and 3 weeks after surgery was 100%(14/14),the rate of granulation hyperplasia at 4 weeks after surgery was 71.4%(10/14),the rate of scar stricture was 21.4%(3/14),granulation hyperplasia and scar stricture at the same time was 7.1%(1/14).Conclusions:Granulation hyperplasia and scar stricture are the two type of benign benign airway stenosis after tracheal wall trauma in rabbits.Injuring cartilage and perichondrium are the key factor for benign airway stenosis.The possibility of airway stenosis through injury to airway mucosa is minimal,chronic persistent injuring of tracheal mucosal may aggravate the degree of airway stenosis on the basis of cartilage destruction.Part 2 To investigate the expression of IL-8,MMP-9 and NCAM-1 in different types of tracheal stenosis in rabbitsBackground and objective:Interleukin-8(IL-8)is a cytokine of the chemokine,which is not only involved in the regulation of inflammatory response,but also has been reported to play an important role in the pathogenesis of a variety of fibrosis diseases.Matrix metalloproteinase-9(MMP-9)belongs to the matrix metalloproteinase family and is involved in the degradation of extracellular matrix,which is closely related to diseases such as pulmonary fibrosis,renal fibrosis and myocardial fibrosis.The neural cell adhesion molecules-1(NCAM-1),also known as CD56,is involved in the immune regulation of the body and plays an important role in the occurrence of tumors and autoimmune diseases.Methods:Using the method of enzyme-linked immunosorbent(ELISA)detection of IL-8 in 15 rabbits of tracheal tissue(the group of E),which the type of stenosis was granulation hyperplasia,MMP-9 and NCAM-1 in 19 rabbits of tracheal tissue(the group of F),which the type of stenosis was scar stricture,and compared with its concentration in normal tracheal tissue.Statistical analysis the expression of three cytokines between in tracheal tissue lesion and the normal tracheal tissue.Results:1.The expression of IL-8 in the trachea tissue of granulation hyperplasia was higher than in the normal control group(P<0.05).The expression of MMP-9 and NCAM-1 in the tracheal tissue of scar stenosis was higher than the normal control group(P<0.05).2.In the rabbit's tracheal tissues with scar stenosis,the MMP-9 value of the stenosis segment/normal segment was correlated with the ratio of NCAM-1 between the two tracheal tissues,and the correlation coefficient was 0.489(P<0.05).Conclusion:(1)IL-8,MMP-9 and NCAM-1 were involved in the formation of stenosis in different forms after the rabbit tracheal wall inj ury.(2)The changes of MMP-9 and NCAM-1 in the formation of scar stenosis after tracheal wall injury in rabbits have a positive correlation,and they may act on the formation of benign tracheal stenosis through relevant pathways.