Objective To observe the effects of intra-articular ozone injection on the secretion of tumor necrosis factor (TNF)-α,Interleukin (IL)-6,IL-17A,and vascular endothelial growth factor (VEGF) in the serum of rats with collagen-induced arthritis (CIA) and explore the therapeutic mechanism of ozone in RA treatment.Methods Thrity-two Wistar rats were randomized into 4 groups,including the ozone groups that receivedintra-articularinjection of 40 μg/ml ozone (O3 group),a blank control group (normal group),a methotrexate (MTX) group (MTX group) anda collagen-induced arthritismodel (CIA group).All the rats,except for those in the blank control group,were subjected to hypodermic injection of bovine collagen Ⅱ and complete Freund's adjuvant to induce CIA.Ozone treatment was administered once weekly for 3 weeks starting at 14 days after the model were established.MTX group were treated with methotrexate 0.9 mg/kg,once a week,a total of three weeks.The swelling degree of the foot were observed,and the serum contents of TNF-oα,IL-6,IL-17A and VEGF were detected.One-way analysis of variance or Kruskal-Wallis test was used to evaluate the experimental data.Results At the end of treatment,the degree of foot swelling was reduced significantly in rats with O3 group compared with that in the CIA group [(4.21±0.14) ml vs (9.12±0.17) ml,t=8.43,P=0.023].The serum concentration of TNF-α,IL-6 and VEGF showed significant difference between the CIA group and the O3 group[91.55(86.55,98.53) pg/ml vs 14.45 (12.55,16.15) pg/ml,x2=6.216,P=0.002;145.08(37.44± 362.82) pg/ml vs 5.84(5.47,15.93) pg/ml,x2=13.136,P=0.004;51.56(46.09,74.10) pg/ml vs.36.22(32.18,41.69) pg/ml,x2=3.732,P=0.002].There was no statistically significant difference between the O3 group and MTX group [14.45(12.55,16.15) pg/ml vs [12.45(11.80,15.60) pg/ml,x2=0.243,P＞0.05;5.84(5.47,15.93) pg/ml vs 7.86(5.25,15.23) pg/ml,x2=0.058,P＞0.05;36.22(32.18±41.69) pg/ml vs 40.17(35.47,50.73) pg/ml,x2=0.516,P＞0.05].The serum concentration of IL-17A showed no significant difference between the normal group,the CIAgroup,the MTX group and the O3 group (F=1.827,P=0.165).Conclusion Intra-articular injecfion of 40 μg/ml ozone can attenuate synovitis in rats with CIA,the mechanism may relate to the inhibition of TNF-oα,IL-6 and VEGF in the serum.

A 58-year-old female patient with systemic lupus erythematosus received an IV infusion of cyclophosphamide for four times (the therapeutic dose of 200, 400, 200, 400 mg, there were 8 days apart between the first and the second medication, there were 12 days apart between the second and the third medication, there were 29 days apart between the third and the fourth medication).There were no symptoms after first administration.On day 2 of the second administration, the patient showed limb shaking and sweating.The serum sodium decreased from 127 mmol/L before treatment to 107 mmol/L.Hyponatremia associated with cyclophosphamide was considered.Continuous intravenous pumping of concentrated sodium 2.3 g was given.Four days later, her serum sodium was 133 mmol/L, concentrated sodium was replaced by oral salt capsules one pill thrice daily.The level of serum sodium decreased slightly after the third and the fourth administrations then returned to normal levels after giving salt capsules.

A 58-year-old female patient with systemic lupus erythematosus received an IV infusion of cyclophosphamide for four times (the therapeutic dose of 200, 400, 200, 400 mg, there were 8 days apart between the first and the second medication, there were 12 days apart between the second and the third medication, there were 29 days apart between the third and the fourth medication).There were no symptoms after first administration.On day 2 of the second administration, the patient showed limb shaking and sweating.The serum sodium decreased from 127 mmol/L before treatment to 107 mmol/L.Hyponatremia associated with cyclophosphamide was considered.Continuous intravenous pumping of concentrated sodium 2.3 g was given.Four days later, her serum sodium was 133 mmol/L, concentrated sodium was replaced by oral salt capsules one pill thrice daily.The level of serum sodium decreased slightly after the third and the fourth administrations then returned to normal levels after giving salt capsules.