Experimental Study On The Therapeutic Effect Of DAla2GIP On Knee Articular Cartilage Injury In APP/PS1 Mice

Objective: 1.To observe the severity of knee articular cartilage injury in APP/PS1 mice;2.To observe the protective effects and potential mechanism of GIP analogue DAla2 GIP on knee cartilage damage.Methods: Twelve 9 months old male APP / PS1 mice and the other 12 male littermate wild-type mice were randomly divided into four groups: The wild-type control group(WT-PBS),the wild type DAla-2GIP treatment group(WT-DAla2-GIP),the APP / PS1 transgenic group(APP/PS1-PBS)and the APP/PS1-DAla2 GIP treatment group(APP/PS1-DAla2GIP).With 6 mouses in each group,WT and APP/PS1 teatment groups were intraperitoneally injected with 1nmol/ml DAla2-GIP 0.2 ml/day for 30 days,WT and APP / PS1 group were intraperitoneally injected with 0.01 MPBS.After 30 days of drug injection,followed by 1% ether anesthesia,the femoral articular surface of the knee was taken off: Using HE staining for morphological observation of articular cartilage,using Safranim O staining for histological score,and TNF-? immunohistochemistry and Col-II,MMP-13 immunofluorescence staining.Results: 1.The HE staining showed that the cartilage of the knee joint was small and thi n,and there was no typical four layer structure,the calcification area is not obvious.2.Safranin O staining showed that four groups have different degrees of decrease of the proteoglycan and that of fibrosis,the more to the condyles,the less of proteogl ycan.OARSI score showed no difference between all groups,but our observations showed tha t the depth and range of fibration of APP/PS1 were significantly higher than those in the control group.3.Immunohistochemistry,immunofluorescence and ELISA revealed that : Compared with the WT-PBS group,the level of TNF-? and MMP-13 of APP/PS1 group were significantly higher(P<0.05.Whereas,the expression of COL-II was lower than that of WT-PBS group(P<0.05).Compared with APP/PS1 group,the expression of TNF-? and MMP-13 decreased significantly in the APP/PS1-DAla2 GIP treated group.however the Col-II protein increased significantly(P<0.05).While there was no significant difference between the WT-DAla2 GIP group and the WT-PBS group(P>0.05).Conclusion: 1.APP/PS1 transgenic mice may happen to articular cartilage damage;2.Increased secretion of inflammatory cytokines such as MMP-13 and TNF-? may lead to the injury of articular cartilage in APP/PS1 transgenic mice;3.The reagent of DAla2 GIP may protect the articular cartilage damage by reduce the secretion of MMP-13 and TNF-? and increase the expression of Col-II,which ma y open up new ways for clinical treatment of OA.