The Effect Of Artesunate On UPA Of Synovium In Rheumatoid Arthritis

Objectives:To investigate the expression of Urokinase-type plasminogen activator(uPA) and its receptor(uPAR) in rheumatoid arthritis (RA) synovium, observe the effect of artesunate (ART) on the expression of uPA in RA synoviocytes, approach the effect of ART on uPA/uPAR pathway, and reveal the effective mechanism of ART in RA.Methods: 1.The expression of uPA and uPAR in RA synovium:(1) 18 RA and 8 OA Synovia were obtained during centesis from patients knee joints and synoviocytes were cultured. Then culture supernatant were collected to detect the level of uPA by ELISA; (2) 18 RA synovial tissues and 10 OA synovial tissues were collected to detect the expression of uPAR by IHC, and the OD value were calculated by Image-propius 5.0 software. 2.The effect of artesunate on the expression of uPA in RA synoviocytes: The 18 RA synoviocytes were stimulated 24h with 5μg/ml LPS, then incubated with ART for 48h. ART concentration were divided into 4 groups: 0 (control group),3.125(a group),6.25(b group) and 12.5μg/ml (c group). The level of uPA in supernatant was detectd by ELISA; the expression of uPA in synoviocytes was detectd by IHC, and the OD value were calculated; the expression of uPA mRNA was detectd by RT-PCR, and the correspondent content were calculated.Result: 1.The expression of uPA and uPAR in RA synovium: (1)The concentration of uPA in RA supernatant was 1.37±0.37 ng/ml, OA was 0.54±0.29 ng/ml, RA was higher than OA(P < 0.05). (2)The OD value of uPAR in RA synovial tissues was 806.53±97.86, OA was 406.71±96.82, RA was higher than OA (P < 0.05) . 2.The effect of ART on the expression of uPA in RA synoviocytes: (1)The concentration of uPA in each group were: control group 3.87±0.25,a group 294.56±18.02,b group 190.15±15.48,c group 107.38±26.91.(2)The OD value of uPA in synoviocytes in each group were:control group 307.79±21.39,a group 294.56±18.02,b group 190.15±15.48,c group 107.38±26.91. (3)The correspondent content of uPA mRNA in synoviocytes in each group were: control group 0.72±0.04,a group 0.57±0.05,b group 0.44±0.06,c group 0.33±0.04.The uPA's protein and gene expression in a,b,c group was significantly decreased compared with control group (P < 0.05) .Conclusion: The high expression of uPA in RA synoviocytes and uPAR in RA synovial tissues shows that uPA/uPAR system plays an important role in the inflam process in RA. ART can inhibit the expression of uPA in a dose dependent manner. It reveals that ART could inhibit the inflam progress in RA by accommodating uPA/uPAR pathway.