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Explore The Expression Of RANKL And Mechanisms Of 1,25-dihydroxy Vitamin D3 To Fibroblast-like Synoviocytes Of IL-22 Mediated In Rheumatoid Arthritis

Posted on:2016-06-18Degree:MasterType:Thesis
Country:ChinaCandidate:J C LiFull Text:PDF
GTID:2284330479992901Subject:Internal Medicine
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Objectives:1.Confirm the role of 1,25(OH)2D3 in rheumatoid arthritis.2.Confirming 1,25(OH)2D3 by blocking "IL-22 ' JAK-2 / STAT-3 and p38 MAPK / NF-κB" pathway, inhibits expression of RA patients FLS RANKL.Methods:1.Collect the clinical data of patients with rheumatoid arthritis, a retrospective analysis of the relationship between 1,25(OH)2D3 and it.2.Detect the expression of FLS RANKL m RNA.(1)Detect the best time of IL-22 stimulate synovial cells.(2)Detect the expression of different concentrations of l,25(OH)2D3, and compared with JAK-2 pathway inhibitor.(3)Detect the expression of different concentrations of l,25(OH)2D3 after the JAK-2/STAT-3 pathway inhibited.(4)Detect the expression of different concentrations of l,25(OH)2D3, and compared with p38-MAPK pathway inhibitor.(5)Detect the expression of different concentrations of l,25(OH)2D3 after the p38 MAPK/NF-κB pathway inhibited.3.Analysis using SPSS 17 statistical software.Result:1.(1)Cases of serum 1,25(OH)2D3 levels were lower than that of the healthy control group(t=-3.19,P<0.05).(2)Serum 1,25(OH)2D3 levels were negatively correlated with age, BMI index and ESR(r=-0.267、-0.377、-0.323,both P<0.05).(3)BMD was classified into three groups:normal,osteopenia and osteoporosis,and significant differences of serum 1,25(OH)2D3 levels were found by comparasion with each group(F=10.174,P<0.01).Osteoporosis serum 1,25(OH)2D3 levels were negatively correlated with ESR(r=-0.451,P<0.01).(4)Serum 1,25(OH)2D3 levels were classified into normal, reduction and deficient groups, and significant differences of serum 1,25(OH)2D3 levels were found by comparasion with each group(F=18.354,P<0.01). Serum 1,25(OH)2D3 levels were negatively correlated with disease duration in the group of reduction serum 1,25(OH)2D3 levels(r=-0.846,P<0.01).(5)Women group’s serum 1,25(OH)2D3 levels were negatively correlated with age, body weight, BMI index, ESR and CRP(r=-0.500、-0.354、-0.432、-0.431、-0.385, both P <0.05). Women’s group’s serum 1,25(OH)2D3 levels were less than those of male group, and significant differences of serum 1,25(OH)2D3 levels were found by comparasion with each group(t=-4.375, P <0.01).2.(1)After pretreat 48 hours and 72 hours, expression of FLS RANKL was significantly higher(P<0.05), and expression of RANKL after 72 hours higher than 48 hours.(2)After IL-22 stimulation 72 hours, add IL-22 and JAK-2 inhibitors group, IL-22 and 1,25(OH) 2D3 lower, middle, higher different concentrations of the group, expression of RANKL with IL-22 were lower than the control group(P<0.05), and the middle group is the lowest of them.(3)After IL-22 stimulation, after the addition of the JAK-2 inhibitor and different concentrations of 1,25(OH) 2D3, the expression of RANKL was higher than that of onlyJAK-2 inhibitor group(P<0.05). There were significant differences between the 3 groups of different concentration groups(F=6.704,P<0.05).(4)After IL-22 stimulation 72 hours, add IL-22 and p38-MAPK inhibitors group, IL-22 and 1,25(OH) 2D3 lower, middle, higher different concentrations of the group, expression of RANKL with IL-22 were lower than the control group(P<0.05), and the middle group is the lowest of them.(5)After IL-22 stimulation, after the addition of the p38-MAPK inhibitor and different concentrations of 1,25(OH) 2D3, the expression of RANKL was higher than that of only p38-MAPK inhibitor group(P<0.05). There were significant differences between the 3 groups of different concentration groups(F=11.333,P<0.05)Conclusions:1.Closely related with 1,25(OH) 2D3 and rheumatoid arthritis are, and it may play a development role.2.There have an inhibitory effection of 1,25(OH)2D3 to RA-FLS RANKL, and especially the middle concentration(1n M) inhibited significantly.3.1,25(OH)2D3 may cloud block "IL-22 ' JAK-2 / STAT-3 " pathway, inhibits expression of RA patients FLS RANKL.4.1,25(OH)2D3 may cloud block "IL-22 'p38 MAPK / NF-κB" pathway, inhibits expression of RA patients FLS RANKL.
Keywords/Search Tags:Rheumatoid arthritis, Vitamin D, 1α,25-Dihydroxyvitamin D3, IL-22, Fibroblast-like synoviocytes
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