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Experimental Study Of Small Molecule Compound Kartogenin On Patellofemoral Joint Degeneration Induced By Patella Baja In Rats

Posted on:2020-06-17Degree:MasterType:Thesis
Country:ChinaCandidate:N LiuFull Text:PDF
GTID:2404330590984816Subject:Surgery
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Objectives The purpose of this study was to investigate the feasibility of a model of patellofemoral arthritis(PFOA)caused by a female Sprague-Dawley(SD)painful ligament shortening,and to use a novel small molecule compound kartogenin.(KGN)Intervened in this model to study the effects of KGN on articular cartilage,synovium,and infrapatellar fat pad(IFP).Methods Thirty 3-month-old SPF female SD rats were randomly divided into 3 groups: control group(Sham group),10 Patellar ligament shortening group(PLS),and 10 patellar ligament shortening + KGN group(KGN group).In the PLS group,surgery was performed only without KGN,and the KGN group underwent surgery and injected KGN into the knee joint cavity.Postoperative KGN rats were injected subcutaneously with KGN at a dose of(50?l/everyone,125 ?mol/L,1/week).The PLS group was given the same amount of normal saline for intra-articular injection.After 8 weeks,the X-ray was used to detect the right knee.Whether it is low in the humerus,followed by anesthesia,abdominal aortic blood,sacrifice,right knee joint collection,specimens were fixed,decalcified,embedded,and sliced.Toluidine blue staining was used to assess the degree of cartilage degeneration;hematoxylin and eosin staining(HE staining)staining was used to detect synovitis and IFP degradation;immunohistochemical staining was used to detect tibia and femoral trochlear cartilage Collagenase II(COLII),aggrecan(AGG),matrix metalloproteinase-13(MMP-13),disintegrin and metalloproteinase with platelet 4(a disintegrin and metalloproteinase with Expression of thrombospondin motifs 4,ADAMTS-4)and smooth muscle actin(SMA)in human caspase-3 and IFP;detection of cartilage by enzyme-linked immunosorbent assay(ELISA)Cartilage oligomeric matrix protein(COMP).Each group of data was collected for statistical analysis.Results 1 The patella baja of the X-ray examination: Compared with the Sham group,the sacrum of the PLS group was significantly lower than that of the sham group(P<0.05),while the PLS group had no significant difference in the patella position compared with the KGN group.2 Gross: There was no change in the sham group;the cartilage degeneration was significantly higher in the PLS group than in the sham group,and the OARSI score was significantly higher(P<0.05);the KGN group was significantly lighter than the PLS group,but the OARSI score was significantly lower.There was no statistical difference(P>0.05).3 Toluidine blue staining: The cartilage in the Sham group and the humeral load-bearing area was smooth and complete,the cartilage matrix was evenly and deeply stained,and the cartilage was almost not degenerated.Compared with the Sham group,the cartilage and the humeral load-bearing area of the PLS group were extensively swollen and damaged.Cleavage and even exfoliation,cartilage matrix staining was light,chondrocyte number decreased,trochlear cartilage degeneration was obvious,OARSI score was significantly increased(P<0.05);KGN group compared with PLS group,cartilage inflammation and damage in trochlear and humerus bearing area The cleft palate was lighter,the cartilage matrix was darker,the number of chondrocytes was higher,the degree of cartilage degeneration was lighter,and the OARSI score was significantly lower(P<0.05).4 HE staining results:Synovial membrane: Sham group was evenly stained,the thickness of synovial membrane was normal,the number of cell layers was 1-2 layers,and there was no inflammatory cell infiltration;the PLS group was thicker than the sham group,the number of cell layers was > 4 layers,under the synovial membrane.Tissue hyperplasia and massiveinflammatory cell infiltration,OARSI score was significantly increased(P<0.05);KGN group and PLS group,the synovial membrane was thinner,the number of cell layers was 3-4 layers,subarachnoid tissue hyperplasia and a small amount of inflammatory cell infiltration The OARSI score was significantly lower(P<0.05).IFP: sham group without fibrosis and inflammatory cell infiltration;PLS group compared with sham group,IFP full of fibrotic lesions,fat cells disappeared,accompanied by a large number of chronic inflammatory cell infiltration,synovial membrane and lower connective tissue necrosis,OARSI score significantly increased High(P<0.05);compared with the PLS group,the IGF-filled fibrotic lesions were milder in the KGN group,with a small number of adipocytes,accompanied by mild chronic inflammatory cell infiltration,and the OARSI score was significantly lower(P<0.05).5 Histochemical staining results:Expression of cartilage metabolism markers: PLS group VS Sham group,COLII decreased significantly(P<0.05),AGG decreased significantly(P<0.05),MMP-13 increased significantly(P<0.05),ADAMTS-4 increased significantly(P<0.05)),caspase-3 increased significantly(P<0.05);KGN group VS PLS group,COLII increased significantly(P<0.05),AGG significantly increased(P<0.05),MMP-13 decreased significantly(P<0.05),ADAMTS-4 The expression was significantly decreased(P<0.05),and the expression of caspase-3 was significantly decreased(P<0.05).Soft tissue around the joint: The number of blood vessels in the middle of IFP represents the degree of IFP inflammation,and the degree of IFP inflammation in the PLS group vs.Sham group was significantly increased(P<0.05).Compared with the PLS group,the degree of IFP inflammation was significantly reduced in the KGN group(P<0.05).6 The results of ELISA:Compared with the Sham group,the serum cartilage catabolic marker COMP was significantly increased in the PLS group(P<0.05).After KGN interference,the COMP was significantly lower in the kartogenin group than in the PLS group(P<0.05).Conclusions Patellar ligament shortening can successfully establish a rat PFOA model,resulting in soft joint degeneration,inflammation of the synovium around the joint and degradation of IFP.KGN intervention can delay the injury of rat PFOA cartilage induced by patellar ligament shortening,and reduce the degree of inflammation of synovium and IFP around the joint.Figure13;Table5;Reference 145...
Keywords/Search Tags:KGN, patellofemoral joint, OA, cartilage, synovial membrane, IFP
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