| Objective:Establishing a model of primary adjuvant-induced arthritis(AA)in SD rats to study the effects of the high,medium and low doses of Geniopicroside GPS on foot thickness,foot circumference,foot volume,ALT,AST levels,synovial tissue IL-6,TNF-α levels for AA rats.Studing the protective effect of GPS on arthritis of AA rats by pathologic examination and X-ray experiment.Methods : To arthritis modeling for rats by intradermal injection of 0.1 ml Freund’s complete adjuvant(FCA)to the right hind toe of SD rats.Successful SD rats were randomly divided into 5 groups: blank group,Freund’s complete adjuvant-induced arthritis model group,GPS high-dose group(120 mg/kg),GPS medium-dose group(60 mg/kg),the low-dose group(30mg/kg)and the positive control methotrexate(MTX)group(0.2mg/kg),the rats were given oral administration of different doses according to the experimental design within d1-d7 after successful inflammation.Primary lateral foot thickness,foot circumference and foot volume of rats were measured by vernier caliper and toe volume meter every day,to evaluate the foot swelling in rats.The pathomorphological changes of ankle were observed under a light microscope.The levels of IL-6,IL-4,TNF-α,ALT/GPT and AST/GOT were measured by Enzyme-linked immunosorbent assay(ELISA).Results:Therapeutic effect of each administration group on AA ratsThree days after model establishment,the posterior paw of the AA rats showed obvious swelling,erythema,inconvenience and other symptoms.The synovial membrane of the AA rats showed obvious hyperplasia,disordered distribution,accompanied by a large number of inflammatory cell infiltration and pannus formation.Continuous administration for 7 days,the high,medium and low doses of GPS(120mg/kg,60mg/kg,30mg/kg)and MTX(0.2mg/kg)can improve the AA rat foot swelling and alleviate synovial tissue inflammation in various degrees,and the anti-inflammatory effect of the low-and medium-dose GPS group(3omg/kg,60mg/kg)were more significant(120mg/kg)(P<0.01).Inhibition of bone destruction in AA rats by each administration groupCompared with the normal group,the joints of the AA group showed swelling,bone destruction,and a large gap between the toes.Compared with the AA group,theGPS(30,60,120 mg/kg)group reduced joint swelling,bone destruction,and a small gap between the toes.It can be seen that gentiopicroside has a certain anti-inflammatory effect on rat adjuvant arthritis.Down-regulation of ALT and AST in serum of AA group rats by each administration groupIn this experiment,ALT and AST in the serum of rats were measured.Compared the normal group,it was found that AST and ALT in the AA group significantly increased compared with the normal group.It indicated that the adjuvant caused certain damage to the liver of rats.Compared with AA group,GPS(30,60,120 mg/kg)showed that the contents of AST and ALT decreased,which indicating that gentiopicroside has anti-inflammatory effects.Compared with the GPS(120mg/kg)group,the AST and ALT levels in the high-dose group were down-regulated,compared with the high-dose GPS group(P<0.05,P<0.01),the high-dose group showed hepatoprotective effects.Down-regulation of TNF-α and IL-6 in synovial tissue of AA group rats by each drug-administered groupIn this study,the changes of TNF-α and IL-6 levels in the synovial tissue of rats were analyzed.The levels of TNF-α and IL-6 in the synovium of each group were compared with those in the normal group,it found that TNF-α and IL-6 levels were up-regulated(P<0.01)in AA group.However,the levels of TNF-α and IL-6 were down-regulated in the GPS(30,60,120 mg/kg)group compared with the AA group(P<0.01,P<0.05).It indicated that gentiopicroside has good anti-inflammatory effects on adjuvant arthritis in rats.Conclusion : The low-and medium-dose GPS(GPS: 30mg/kg,60mg/kg)alleviated the inflammatory symptoms of AA rats higher than the high dose of GPS(120mg/kg),this indicating that the anti-inflammatory treatment effect of GPS on AA rats is related to dose.The medium dose has better anti-inflammatory effect.From the analysis of AST,ALT and TNF-α,IL-6,it can be seen that GPS(30,60mg/kg)has a certain inhibitory effect on inflammation in rats,and GPS(120mg)/kg)high dose group also showed liver protection. |
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