| Compound gout granules are composed of Anemarrhena,cassia twig,ginger,wind and other Chinese herbal medicine composition.A well-known old expert in a Chinese medicine hospital in Shandong province has used the experience prescription for the treatment of gouty arthritis for many years,Chinese medicine granule preparation is de-veloped according to this experience prescription.In this study,a variety of animal models were used to study the pharmacodynamics and mechanism of the drug.Objective.The effect of compound Gout Granules on acute gouty arthritis was observed in two models of acute gouty arthritis in rabbits and rats,The antiphlogistic analgesic effect was investigated by four methods of the acute inflammatory model,mice ear swelling,mouse hot plate and writhing analgesia,Through the above six models,the anti-gout mechanism of compound gout particles was discussed and the experimental basis was provided for the clinical application.Method 1.Effect of compound gout granules on acute GA in rabbits induced by MSU:Compound gout granules were continuously administered 21d,The 20th day two hours after of administration,The GA model was prepared by injection of 0.4 ml of 80 mg/ml MSU suspension in the joint cavity of rabbits,The same model was prepared in 21d.The degree of joint swelling was measured at 1,3,5,24,and 29h after the first inflammatory;at the last time of inflammatory 5h,the number of WBC and PGE2 content in the joint fluid were measured,determine the level of 5-HT、IL-1β、IL-8 in joint synovial tissues,histopathological examination was performed at the same time.2.Effect of compound gout granules on acute GA induced by MSU in rats:the compound gout granules were continuously administered 2 days.The GA model was prepared by the 0.2 ml of 2.5 mg/ml MSU suspension was injected into the ankle joint of rats immediately.The right posterior foot volume of rats at 1,3,5 and 24h were measured before and after modeling.Rats were anesthetized and blood was drawn,serum uric acid and PGE2 levels were measured.3.Effect of compound gout granules on carrageenin induced paw swelling in rats:Compound gout granules were continuously administered 21d,2h after the last dose,rats foot metatarsal were subcutaneously injected with 1%carrageenan 0.1 ml,1%carrageenan induced swelling of sole plantar.The right hind foot volume of rats was measured in 1,2,3,4 and 5h before and after the model establishment.4.Effect of compound gout granules on ear swelling induced by xylene in mice:Compound gout granules were continuously administered for 14 days.2h after the last administration,Use a microsyringe to absorb 25μl 100%xylene on the inner surface of the right auricle,left ear as a blank control.After 15min,the mice were killed by dislocation.The ears were cut.Make the circular ear slices at the same place with 8mm punch and weigh it.The swelling degree and the inhibition rate of swelling were calculated,and the effect of the medicine on the acute inflammatory reaction was evaluated.5.Effect of compound gout granules on hot plate method in mice:Compound gout granules continuous administration of 14d.Each group was treated with 2h at the end of the last dose,and placed on the hot plate(55+0.5 ℃)before heating,and the pain threshold was recorded by licking the foot as the index of pain response.The pain threshold of each mouse was measured 2 times(interval 10min),and the average value was determined.6.Analgesic effect of compound gout granules on writhing test in mice:Compound gout granules were continuously administered 15d.2h after each group was given,0.65%acetic acid solution(0.1 ml/10 g)was injected into abdominal cavity,and the number of writhing reactions of mice in each group was recorded after injection of 15min.Result 1.MSU induced rabbit acute GA test:Compound gout granules high dose 3.0 g/kg/d,medium dose 1.5 g/kg/d,compared with the model control group,model 1,3 and 5h of rabbit articular swelling significantly reduced(P<0.01,0.05),synovial fluid leukocyte number was significantly reduce(P<0.01,0.05),inflammatory cytokines decreased IL-1β significantly(P<0.05),PGE2,5-HT,IL-8(P>0.05)has no obvious effect.The pathological scores of the high,middle and low doses(3,1.5 and 0.75 g/kg)of the compound gout granules were lower than that of the model control group,the lesions were alleviated,but there was no statistically significant difference(P>0.05).anti-inflammatory effect of medium dose 1.5 g/kg/d is slightly better than Tongfengding 0.18 g/kg,slightly lower than the colchicine 4×10-5 g/kg,showed no significant difference(P>0.05).2.MSU induced acute GA test in rats:Compound gout granules high,medium and low dose of 6.8,3.4 and 1.7 g/kg/d compared with the model control group,high dose group of the animal at 3,5,24h after building model significantly reduce joint swelling degree(P<0.01,0.05),model 3h inhibition rate reached a maximum value of 59.6%;in the medium dose group in the model 24h joint swelling was significantly alleviated(P<0.05),the maximum of inhibition rate reached 35.9%;low dose group joint swelling visible reduce but no significant difference was found(P>0.05).High and medium dosage can significantly reduce serum uric acid level and inflammatory factor PGE 2(p<0.01,0.05),colchicine positive control group can significantly reduce inflammation factor PGE 2(p<0.05),colchicine and gout positive control group has no significant effect on serum uric acid(p>0.05).The medium dose of 3.4 g/kg decreased the serum uric acid levels and PGE2 slightly better than the gouty 0.4 g/kg and colchicine 8.0×10-5 g/kg,showed no significant difference(P>0.05).3.Carrageenan induced rat paw edema test:Compound gout granules with high doses of 6.8 g/kg/d compared with the control group,1h and 5h after building model showed significantly inhibited paw swelling(P<0.01,0.05),model 2,3 and 4h swelling visible alleviate but there was no statistical difference(P>0.05),1h after model the highest inhibition rate was 77.3%.The anti-inflammatory effect of the medium dose 3.4 g/kg was equal to Tongfengding 0.4 g/kg,4h anti-inflammatory effect is weaker than ibuprofen 0.07 g/kg(P<0.05),the rest time the anti-inflammatory effect is slightly weaker than of ibuprofen 0.07 g/kg but there was no statistical difference(P>0.05).4.Xylene induced ear swelling in mice:high and medium doses of 13.4,6.7 g/kg/d,compared with model control group,can significantly reduce the degree of swelling of the auricle(P<0.01,0.05),the inhibition rate was 60%and 45.9%.The effect of medium dose of 6.7 g/kg was similar to that of gouty 0.8 g/kg and ibuprofen 0.13 g/kg.5.Mice hot plate analgesia test:high and medium doses of 13.4,6.7 g/kg/d,compared with model control group,had obvious analgesic effect,and the pain threshold of hot plate mice increased significantly(P<0.01,0.05).The effect of medium dose of 6.7 g/kg was similar to that of gouty 0.8 g/kg and ibuprofen 0.13 g/kg.6.The writhing test of mice:the high and medium doses of 13.4 and 6.7 g/kg/d had obvious analgesic effect compared with the model control group,and the number of writhing times of mice caused by acetic acid was obviously reduced(P<0.01,0.05).In the medium dose effect of 6.7 g/kg was equal to the ibuprofen 0.13 g/kg,and was less than Tongfengding 0.8 g/kg,no statistically significant differences(P>0.05).Conclusion 1.Compound gout granules(equivalent human dose 80 40g/d)has significant anti inflammation effects induced by MSU in rabbits,acute GA rat model,xylene induced mouse ear acute inflammation,has obvious analgesic effect on the hot plate,the pain model of mice induced by acetic acid.When the compound Gout Granule is equivalent to the human consumption of 80g/d,it has significant anti-inflammatory effect when the acute inflammatory model of the foot swelling induced by carrageenan in rats.Studies have shown that compound Gout Granule is effective in the treatment of acute gouty arthritis.2.Mechanism of action:Compound gout granules(equivalent to human dose of 80,40g/d)by reducing uric acid levels in blood and the production of inflammatory cytokines IL-1βreduce,play a good anti-inflammatory and analgesic effects.3.Comparing with other drugs:The acute GA test in rabbits and mice induced by MSU shows that effect of this product(rabbit:1.5 g/kg,rat:3.4 g/kg)is slightly worse than that of colchicine(in rabbits:4.0×10-5 g/kg rats:8×10-5 g/kg)and slightly better than Tongfengding(rabbits:0.18 g/kg,rats:0.4 g/kg).The acute inflammation test in rats treated with carrageenin showed that the anti-inflammatory effect of 3.4 g/kg was weaker than that of ibuprofen 0.07 g/kg,which was similar to that of 0.4 g/kg.Xylene induced mouse ear swelling test showed that the anti-inflammatory effect of this products was equivalent to Bloven and Tongfengding,analgesic test showed that this function of product was equal to Bloven,and is slightly lower than Tongfengding(mice analgesic test,this product:6.7 g/kg,Bloven:0.13 g/kg,Tongfengding:0.8 g/kg). |
PDF Full Text Request