Effects Of Ibuprofen Anti-Inflammatory Agent On The Structure And Cytokines Of The Rabbits' S Patellar Tendon And Bone-Tendon Junction

Purpose: We aimed to explore the pathogenensis and healing mechanism of patellar tendinopathy using our established overuse-induced injury animal model by repetitive jump training.In addition,we observed the effects of ibuprofen anti-inflammatory agent on bone-tendon junction structures and cytokines from the perspective of para-inflammation,extracellular matrix degradation and synthesis and discuss the mechanism.Methods: Sixty-eight New Zealand rabbits were randomly divided into four groups: the rabbits' bilateral posterior limbs without any interventions as controls,jump training group,jump training and ibuprofen group and only ibuprofen group.Each group was subdivided into four groups according to different duration time.The Part One was intersted in the bone-tendon junction while the Part Two was about the patellar tendon,and the Part Three was designed to reveal the correlations between the two position.Jump training was conducted on force plate and force and momentum were documented.After harvested,bone-tendon junction specimen were performed histological and immuno-staining including fibrocartilage thickness,cell density,TNF?,HMGB1,MMP-1,MMP-2,Beclin-1,LC3 B,IL-1?,COX-2,PTGES2,COL-I,COL-III while patellar tendon specimen were measured protein level and m RNA for parts of cytokines.Results:(1)OJ4W group had significantly lower average jumping momentum than the OJ2 W group;(2)histological evidence indicated that compared with CON group at the same time point,OJ group demonstrated higher cell density and thicker fibrocartilage zone,abnormal cell morphology and uneven profile,and disappeared tidemark and lose of the highly-ordered hierarchical structure;(3)IHC results showed that compared with CON group at the same time point,the OJ2 W and OJ4 W group had significant increased TNF?,IL-1?,COX-2,PTGES2 and MMP2(P<0.05).;the OJ6 W group had elevated IL-1?,COX-2,MMP2,COL-III(P<0.05).;the OJ8 W group had remarkably increased IL-1?,COX-2,COL-I but decreased MMP1,Beclin(P<0.05);Compared with the OJ group at the same time point,the JAD 2W group had significantly decreased COX-2,PTGES2,MMP2;the JAD6 W group had significantly decreased MMP1,COL-I,COL-I/COL-III,LC3 B and the JAD8 W group had significantly decreased HMGB1,MMP1,COL-I,LC3B(P<0.05).Conclusions:(1)With the jump loading accumulated,rabbits' patella patellar-tendon junction demonstrated a typical pathological changes,and the cytokines also presented time-dependent characteristics.IL-1?,COX-2 and MMP2 remained at a relatively high level and dominated the injury process,TNF? and PTGES2 was rather high till 6W and thereafter downwards.HMGB1 was all the ways low and MMP1 was inhibited till 8W.(2)The inflammatory response taken place in the early phase was beneficial to healing while prolonged inflammatory response was harmful.(3)The ibuprofen had weak inhibit effect on the TNF? and IL-1? but targeted on the COX-2 and PTGES2 well,by which regulated the ECM degradation and formation via suppressing the MMPs and collagen synthesis.Taking Ibuprofen for long time might inhibited the expression of COL-I m RNA in patellar tendon and MMP1 expression in bone-tendon junction,resulting in abnormal collagen synthesis and degradation.(4)The patellar tendon was significantly more capable to mechanical loading than the bone-tendon junction,which might account for higher prevalence rate at the junction.