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The Animal Experiment And Clinical Research Of Tanshinone ?A For The Treatment Of Tendon Adhesions

Posted on:2018-11-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:H LuFull Text:PDF
GTID:1314330515959554Subject:Clinical medicine
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Introduction and Objective:Tendon adhesion refers to the tendon injury during repair of the surrounding tissue proliferation and invasion,resulting in tendon motor dysfunction.Postoperative traumatic tendon adhesion is a common problem after tendon injury,so far there is no effective solution,there are still about 30 to 40%of patients with poor mobility after surgery,hand function and other complications[1].We hope to solve this problem by studying the mechanism of tendon adhesion.Tendon adhesion may occur due to mechanical and chemical damage.Damage induced mesenchymal cells and mast cells release a variety of active substances,so that the organization produces inflammatory response,increased capillary permeability,a large number of slurry exudation.These exudates such as can't be decomposed and absorbed,then promote the accumulation of fibrin,followed by infiltration of fibroblasts and the growth of new capillaries,and finally the formation of fibrous adhesions[2].At present,the healing of the tendon by the inside and outside the two repair mechanisms to complete.Endogenous repair mechanism refers to repair tendon by tendon cell proliferation repair;exogenous repair mechanism refers to the proliferation of tendon through tendon tissue hyperplasia,fibroblasts,inflammatory cells repair damage.The strength of the tendon itself depends mainly on endogenous repair mechanism;and exogenous repair is mainly formed adhesions[3?4].As the inflammatory response leading to increased exudation of local tissue,inflammation of the machine after the more severe tendon adhesion,which is tendon tendon repair is easy to extensive adhesion of the main problems151.TGF-?1/Smad3 is an important signaling pathway in wound repair.TGF-(31 is one of the factors that cause pathologic fibrosis in various tissues after injury.The present study found that tendon injury,TGF-?1 can stimulate the tendon cell DNA synthesis and promote tendon cell proliferation involved in the repair of tendon,to promote fibroblasts and macrophages recruitment,angiogenesis,stimulate collagen production[6].Tanshinone IIA,is an effective component of Salviamiltior-rhiza bunge.It has the functions of anti-bacterial,anti-inflammatory,dilatation blood vessel and anti-platelet agglutination to treat cardiovascular diseases such as coronary heart disease[7-9].We investigated whether TSA can effectively prevent tendon adhesion and its possible mechanism of action,including microRNA(miRNA)and protein expression through TGF-?/Smad signaling pathway,and further validated and applied in clinical practice.The successful implementation of this study will provide a new theory and method for the repair of tendon function.Part I Tanshinone IIA Prevent Tendon Adhesion in the Rat Achilles Tendon ModelBackground:Tendon adhesion between the sheath and tendon surface is a common clinical problem.Orthopedist makes the improvement of repair techniques and rehabilitation to treat tendon adhesion,but it fails to cure completely.TSA was one of the major active phytochemicals because of its anti-inflammatory activity.We used tanshinone IIA(TSA)for the prevention of tendon adhesion in the rat Achilles tendon model and investigated the possible mechanisms,including microRNAs(miRNAs)and protein expression via TGF-?/Smad signaling pathway.Method:Sprague-Dawley(SD)rat Achilles tendons were injured and sutured by a modified Kessler's technique with TSA and normal saline for control.Macroscopic and histological evaluations were applied to examine the injured tendon six weeks after surgery.We evaluated the degree of adhesion in Gross observation and the remodeling of collagen fibers by observing microscopically and determining the amount of scar formation.The expression of microRNAs(miRNAs)was quantified by real-time PCR detection and protein expression were quantified by western blotting detection.Results:In gross evaluation of tendon adhesion,the TSA group had less adhesion appeared.No evidences of tendon rupture or local infection were observed.The content of collagen fibers in tendon tissue was decreased in TSA group compared with the control group,it indicated a significant difference from the control group,P = 0.0004.The expression of miRNAs including miR-155,miR-29b,miR-21,miR-133b and let7 were detected in the repaired tendon tissue,and only miR-29b treated with TSA was observed significantly higher than control group,P<0.0001.The protein expression of TGF-?1 and p-Smad3 treated with TSA was lower than control group.Conclusions:The usage of TSA may be an efficient approach for preventing tendon adhesion.Part II Study the clinical effect of applies salvia miltiorrhiza to prevent metacarpophalangeal joint adhesionHand injury likely to cause postoperative metacarpophalangeal joint adhesion,joint mobility is limited.Especially in patients with post-traumatic metacarpophalangeal joint stiffness,because the activity of the metacarpophalangeal joints on the finger function of a larger impact,so how to restore the hand metacarpophalangeal adhesions in patients with postoperative hand function and improve the quality of life is of great significance.From the September 2015 to March 2016,80 cases of metacarpophalangeal joint fracture patients were randomly divided into two groups.The clinical efficacy of tanshinone IIA(TSA)in prevention and treatment of metacarpophalangeal joint adhesions was reviewed by reviewing the clinical data.The report is as follows.Objective:To investigate clinical effect of applies salvia miltiorrhiza to prevent metacarpophalangeal joint adhesion.Methods:From the September 2015 to March 2016,We conducted 80 cases of metacarpophalangeal joint fracture patients a double-blind,randomized,trial in two groups,salvia miltiorrhiza group were 40 cases,blank control group were 40 cases.58 cases of male and female 22;Average age 20 to 55 years old,38 years old.The thumb joint from 16 cases,24 cases of finger ring refers to the 22 cases,,middle finger in 11 cases,7 cases of his pinky.Causes:machine 33 cases,sports injury 21 cases,car accident injury of 17 cases,9 cases of knife cuts.Before and after treatment for 3 months and 6 months to evaluate imaging,functional assessment of Hand motion TAM system evaluation method(total active movement,TAM),daily life Hand function assessment using the Michigan Hand function assessment(Michigan Hand Outcome Questionnaire and MHQ),The rank sum test(the Mann-Whitney Test),score data using independent sample t Test the statistic method was measurement data and respectively adopted the matched t-test.Results:The incision were all stage I healing,no postoperative complications such as internal fixation loosening or breakage,fracture non-union.All patients were followed up for 6-24 month follow-up,.At latest follow up,TAM score salvia miltiorrhiza group of excellent in 27 cases,good in 10 cases an 3 cases,poor in 0 cases,the excellent and good rate was 93%;Blank group excellent in 15 cases,good in 16 cases and 9 cases,poor in 0 cases,the excellent and good rate was 83%,compare the differences between groups was statistically significant(P<0.05);MHQ scores salvia miltiorrhiza group 60.0±14.2 points,blank group 50.1±15.7 points.Compare the difference between groups was statistically significant(t = 2.96,P<0.05).Conclusion:Applies salvia miltiorrhiza can reduce reduce the degree of postoperative metacarpophalangeal joint adhesion,the clinical effect was satisfied.Part ? Preliminary Study of Tanshinone ?A Combined with Swanson Artificial Joint Replacement in the Treatment of Severe Metacarpophalangeal Joint AdhesionSwanson artificial joints were originally used for joint replacement of the proximal interphalangeal joint(PIP)and the metacarpophalangeal joint(MCP).Previous studies have focused on the clinical efficacy of Swanson artificial joint replacement in the treatment of rheumatoid arthritis[10-12].For the treatment of post-traumatic metacarpophalangeal joint stiffness in patients with a lack of systematic clinical research.Taking into account the current postoperative severe metacarpophalangeal joint adhesions and stiffness in patients with poor clinical outcomes,we choose to use tanshinone II A Joint Swanson joint replacement to solve this problem.And to evaluate their clinical efficacy and subjective evaluation.Objective:To evaluate the efficacy of tanshinone ?A combined with Swanson artificial joint placement in the treatment of severe metacarpophalangeal joint adhesions and stiffness after trauma.Methods:From September 2014 to July 2015,patients treated with tanshinone IIA combined with Swanson artificial joint replacement were retrospectively studied in patients with severe metacarpophalangeal joint adhesions.Including 3 males and 1 female.The index finger was 2 cases,the middle finger was 1 case,and the index finger and middle finger were involved in 1 case.Metacarpophalangeal joint off three people,the hands shut down crush injury 1.The mean age of the patients was 52.15 ± 2.6 years(range 41 to 67 years).The data included preoperative and postoperative scores(grip strength,range of motion of the joints,Sollerman hand function test,and Michigan Hand Outcome Questionnaire,MHQ).Results:The follow-up time was 6 months.(4.2 ± 2.2 kg preoperatively,6.7 ± 2.8 kg postoperatively,P = 0.027).The extent of joint motion was significantly increased(24.6±9.0 preoperatively,47.0 ± 10.7 postoperatively,P<0.001).There was no statistically significant difference between the Sollerman score before and after the procedure(Table 4.1).The total score of MHQ was significantly increased(50 ±15 preoperative,57 ± 15,P = 0.002).Functional aspects,such as daily life,appearance and full patient satisfaction score also increased significantly after surgery.However,daily work and pain did not improve postoperative scores.All patients had improved postoperative appearance and self-satisfaction.Conclusion:Tanshinone ?A combined with Swanson artificial j oint replacement can significantly improve the range of motion of the metacarpophalangeal joint stiffness.Patients hands aesthetic function and have been improved.Future long-term follow-up will help to better determine the efficacy of the method.We suggest that patients with post-traumatic stiffness of the metacarpophalangeal joints can choose tanshinone ?A combined Swanson artificial joint replacement of this operation.4 total conclusionIn rat Achilles tendon injury model,we confirmed that TSA can inhibit the expression of collagen through TGF-?/Smad protein pathway,thus reducing the formation of adhesion.For patients with metacarpophalangeal joint adhesions after hand trauma,the use of intra-articular injection of TSA can reduce the degree of postoperative adhesions metacarpophalangeal joint fracture treatment of postoperative traumatic joint stiffness,Exercise effect,reduce the burden of patients and the country's social and economic,worthy of clinical promotion.For severe metacarpophalangeal joint adhesions patients,we use tanshinone ? A joint Swanson artificial joint replacement can significantly improve the range of motion of patients with metacarpophalangeal joint stiffness.Patient hand aesthetic functions and improved long-term follow-up will help to better determine the efficacy of the method.The whole study systematically and stepwise evaluated the tanshinone ?A treatment of hand tendon adhesion in animals and clinical trials,the clinical efficacy is reliable,no significant complications,technology and drug safety and reliability.It provides a new theory and method for the repair of tendon function,which can be popularized in the future clinical treatment.
Keywords/Search Tags:tanshinone type IIA, Tendon adhesion, miRNAs, Signaling pathways, salvia miltiorrhiza, joint adhesion, Metacarpophalangeal joint, replantation, swanson implant, arthroplasty
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