The effect of intraperitoneal injection of arsenic trioxide on serum RANKL/OPG system in collagen induced arthritis rats / 中华风湿病学杂志

ABSTRACT

Objective To assess the improvement of articular symptoms on collagen induced arthritis (CIA) rats after injecting arsenic trioxide (ATO) intraperitoneal and observe its effects on serum RANKL, OPG on CIA rats and discuss the possible mechanism on RANK/RANKL/OPG system.Methods Numberd twentyeight Wistar rats with correspond weight and age consecutively, then using random number table select 8 rats as blank control group A.Another other 20 as model group (16 wistar rats are established as CIA models by immunized twice with bovine type Ⅱ collagen and Freund's complete adjuvant emulsion).Using ranllm numbor table divided CIA rast into the CIA model control group B (n=8) and ATO treatment group C (n=8) randomly.After grouping for 3 days, ATO treatment group were injected with ATO liquid intraperitoneally for 1 week (dose of 4 mg· g-1·d-1, last 1 day raise to 8 mg/kg).Serum were collected after 3 days , while rates in the control group were given same quantity of saline solution with the same method.Arthritis index (AI) and X-ray radiography were assessed for limb joint damage.Flow cytometry (FMC) was used to detect chemokines quantitatively of each rats serum, including Nuclear factor kappa B ligand receptor activation factor/bone protection predominate (RANKL/OPG).According to the data distribution, t test or Wilcoxon test were used to compare the difference between groups.Results ① After administration with ATO for 1 week arthritis index of group C reduced significantly than the CIA model group (2.63±0.92, 6.62±0.91, t=8.73, P＜0.01), and X-ray showed joint damage alleviated.② The serum level of RANKL in the CIA model group was significantly higher than the blank control group [(1 890.70(797.03, 10 571.94) pg/ml, 74.46(29.21, 95.37) pg/ml, T=43, P=0.005];③ The serum level of RANKL in the ATO treatment group was significantly lower than the CIA model group [44.78 (21.41, 79.83), 1 890.70 (797.03, 10 571.94), T=47, P=0.01].④ There was no statistically significant difference of the Serum OPG level between the three groups [16.87(6.91, 17.64), 5.32(3.42, 33.14),14.24(6.96, 21.86) pg/ml, x2=5.078, P=0.166].Conclusion The inflammatory mediators in the process of bone metabolism of CIA rats is disordered , the most significant presentation is the rise of serum RANKL level.Intraperitoneal injection of ATO could improve the arthritis index of CIA rats and its mechanism may be reducing the concentration of serum RANKL/OPG ratio.