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Effects Of Mechanical Stretch Regulating CREB/TGF-?3 Signaling Pathway On Tendon Healing

Posted on:2021-01-10Degree:MasterType:Thesis
Country:ChinaCandidate:S F LiFull Text:PDF
GTID:2404330611995840Subject:sports Medicine
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IntroductionWith the improvement of living standards and the popularization of sports,tendon injury has become a common problem in daily life.In recent years,the comprehensive treatment of tendon injury has been very mature,but complications after surgery are still difficult to solve,and tendon adhesion is the most prominent problem.Due to the special physiological structure and functional requirements of the flexor tendon,the problem of postoperative adhesion is obvious.Therefore,how to promote the healing of tendons and reduce the formation of scar adhesion is a issue to be solved in clinical work.Common methods include improving hand suture methods,using biophysical barriers,topical application of drugs,and postoperative physical therapy.Among them,early mechanical stretch has been clinically recognized as the main physical therapy method,but the specific mechanism is not clear.Related studies have reported that its mechanism is related to the TGF-? signaling pathway.Studies have shown that transforming growth factor-?1(TGF-?1)is closely related to tissue healing.It plays an important role in the recruitment,proliferation,and secretion of collagen fiber and reconstruction of tendon tissue,but It is also the main cause of scar formation.As an isomer of TGF-?1,TGF-?3 can play the opposite role to TGF-?1 in some respects to prevent the formation of adhesions during tissue repair,but its research on the mechanism of tendon healing is not thoroughly.On the other hand,cAMP response element binding protein(CREB)as a transcription factor is involved in the regulation of TGF-?3 and plays an vital function in the process of tissue fibrosis and scar formation.However,the specific mechanism of TGF-? / CREB signaling pathway behind tendon healing is still unclear,and its relationship with mechanical stimulation has not been reported.Therefore,the research objectives of this subject are: 1.To verify the effect of periodic mechanical stretch on promoting tendon healing and its effect on the distribution of TGF-?1,TGF-?3,and CREB;2.To preliminary investigate the specific mechanism of periodic mechanical stretch on regulating CREB / TGF-? signaling pathway.Material1.Thirty-six healthy male SD rats were divided into 3 groups of 12 rats each randomly.Group A was a stretch group.Rats in this group established bilateral flexor digitorum profundus(FDP)injury repair models,and passive mechanical stretch was continued for 1 week beginning at 72 hours after surgery.Group B was the injury group.Rats in this group established FDP injury models but without intervention;Group C was the sham operation group,which only cut the skin without damaging the tendon or intervene.2.Take samples from coalesced tendon at 1,2,4,and 8 weeks after surgery.Evaluate the therapeutic effect and cell proliferation by anatomical observation,HE staining and,biomechanical test,evaluate the expression of growth factor by real-time quantitative PCR,immunohistochemical staining,and biomechanical detection.Result1.Histological observation showed that the tendon tissue in the stretch group had a more regular arrangement of collagen fibers at the early postoperative stage,and the inflammatory response was reduced.In the injured group,tendon tissue was widely adhered to surrounding tissues,making it difficult to separate and expose.Statistical analysis showed that the stretch group had more excellent marks than injured group at each time points during the healing process.Compared with the injured group,the number of fibroblasts was reduced,the degree of adhesion was reduced,and the tendon had better slide properties(P <0.05).2.Biomechanical tests showed that the biomechanical parameters of the tendons in the stretch group and the injury group were lower than those in the sham operation group,and the differences were statistically significant(P <0.05).With the increase of postoperative time,the biomechanical indicators of the two groups of tendons gradually increased;the biomechanical index of the tendon in the stretch group was slightly lower than that in the injury group,but it was not statistically significant.3.Real-time fluorescence quantitative PCR showed differential expression of TGF-?1,TGF-?3 and CREB in the early stage of the stretch group.The main feature was the high expression of TGF-?3,which lasted for a long time.The expression level of TGF-?1 in stretch group was higher than that in injury group of the same-time in healing process,and the expression levels of TGF-?3 and CREB were lower than those in injury group of the same-time,and the difference was statistically significant(P <0.05).4.Immunohistochemical staining showed that there were time differences in the expression of the three growth factors in the stretch group,and the change of CREB expression was earlier than the changes of TGF-?1 and TGF-?3 expression.Conclusion1.Periodic passive mechanical stretch applied early can promote tendon healing and reduce scar formation.2.Periodic passive mechanical stretch applied early may promote endogenous healing of tendons through TGF-?3.3.There may be TGF-? signaling pathway regulated by CREB to affect the tendon healing process.4.Proper early activities will not reduce the healing strength of the tendon in the process of tendon healing.
Keywords/Search Tags:tendon injury, tissue adhesion, transforming growth factor-beta1, transforming growth factor-beta3, cAMP response element binding protein
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