The Correlation Researh Between DKK1 And TNF-α In Collagen-Induced Arthritis Rats And ⁹⁹Tc-MDP Intervention

Object:To observe the expression of synovial fluid and serum levels of DKK1 and TNF-α, and synovium and cartilage of ankle joints expression of DKK1 and TNF-α in collagen-induced arthritis(CIA) rats. And explore the relationship of that synovial fluid and serum levels of DKK1 and TNF-α in CIA and the possible treatment mechanism of 99Tc-MDP.Method:The CIA model was established by subcutaneous injection with type II collagen and complete Freud’s adjuvant to rats. CIA rats were randomly divided into 4 groups:model group, methotrexate (MTX) group, low dose 99Tc-MDP group, and high dose 99Tc-MDP group. Bone erosion were assessed by Larsen score and histopathological score. The synovial fluid and serum levels of DKK1 and TNF-α were tested by ELISA. The synovium and cartilage of ankle j oints expression of DKK1 and TNF-α was tested by immunohistochemistry. T test, analysis of variance, and correlation analysis were used for statistic analysis.Result:Compared with nomal group, bone erosion, synovial fluid and serum levels of DKK1 and TNF-a, and synovium and cartilage of ankle joints expression of DKK1 and TNF-α in CIA rats were significantly increased (P<0.05). Compared with model group, bone erosion, synovial fluid and serum levels of DKK1 and TNF-α, and synovium and cartilage of ankle joints expression of DKK1 and TNF-α in methotrexate (MTX) group, low dose 99Tc-MDP group, and high dose 99Tc-MDP group were significantly decreased (P<0.05); The serum levels of DKK1 in both 99Tc-MDP groups began to decline at 1 week after intervention (P<0.05), the serum levels of DKK1 in MTX treatment group began to decline at 2 week after intervention (P<0.05), and the serum levels of TNF-α in MTX treatment group and both 99Tc-MDP groups all started to decrease at 1 week after drug intervention (P<0.05). Bone erosion, synovial fluid and serum levels of DKK1, and synovium and cartilage of ankle joints expression of DKK1 in 99Tc-MDP intervention groups were notably lower than those in MTX group(P<0.05), and the indexes in both 99Tc-MDP groups illustrated no significant difference (P>0.05). Moreover, synovial fluid and serum levels of TNF-α, and synovium and cartilage of ankle joints expression of TNF-α in MTX group and both 99Tc-MDP groups demonstrated no significant difference (P>0.05). Correlation analysis showed that synovial fluid and serum levels of DKKl and TNF-a in CIA rats were positively correlated (r=0.439,P<0.05).Conclusion;Compared with nomal group, synovial fluid and serum levels of DKK1 and TNF-α, and synovium and cartilage of ankle joints expression of DKK1 and TNF-α in CIA rats were significantly increased.99Tc-MDP and MTX both can reduce the synovial fluid and serum levels of DKK1 and TNF-α, and synovium and cartilage of ankle joints expression of DKK1 and TNF-α CIA rats. The effect of 99Tc-MDP on inhibiting synovial fluid and serum levels of DKK1 and synovium and cartilage of ankle joints expression of DKK1 was better than MTX. Correlation analysis showed that synovial fluid and serum levels of DKK1 and TNF-α in CIA rats were positively correlated.