Ultrasound Guided Intra-Articular Injection Of Triptolide-Loaded Solid Lipid Nanoparticle For Treatment Of Rabbits Antigen-Induced Arthritis

Objective:To evaluate the efficacy of ultrasound-guided intra-articular injection of triptolide-loaded solid lipid nanoparticle(TP-SLN)for treatment of antigen-induced arthritis(AIA)in rabbits.Materials and methods:Thirty three New Zealand white rabbits were randomly divided into intervention group(n=27)and model group(n=6),and intervention group was divided into triptolide(TP)group(n=7),TP-SLN group(n=7),betamethasone(BS)group(n=7),and dimethyl sulfoxide(DMSO)group(n=6)which were injected intra-articular with TP?TP-SLN?BS and DMSO respectively.AIA model were induced in each group firstly.The injection therapy in intervention group started one week after last immunization in order to avoid irreversible joint damage in the later induction.The ultrasonic scores were assessed in synovitis,synovial blood flow and the bone erosion in rabbits.Meanwhile,the correlation of ultrasonic scores and pathological scores was determined.The efficacy and side effects of each group were assessed by combining ultrasonic scores,pathological scores,behavior,appetite,weight,joint diameter,skin temperature and biochemical examination.Results:(1)The blood biochemical indicators and pathological findings of liver and kidney among each group had no significant difference.(2)The diameter of the knee joint and the skin temperature of rabbits began to increase significantly(all P<0.01)in model group after 1 day of the last induction.All rabbits in model group began to appear synovial hyperplasia and synovial blood flow by ultrasound examination after1 to 2 weeks and bone erosion after 4 weeks.(3)Compared with the model group,the diameters of knee joints in TP group,TP-SLN group and BS group began to reduce after a week of intra-articular injection(P<0.01),however,the body weights of the rabbits and the skin temperature of the knee joints did not change significantly(all P>0.05).(4)Except the DMSO group,other groups in intervention group were effective in treating synovial hyperplasia compared with the model group,with TP-SLN and BS being the best.The ultrasonic and pathological scores in synovitis in TP group were lower than that of model group(Z=-2.726 and-2.082 respectively,all P<0.05),and the ultrasonic scores of BS group and TP-SLN group(Z=-2.176?-2.360respectively,all P<0.05)and pathological scores(Z=-2.687 and-2.082 respectively,all P<0.05).(5)Compared with the model group,the TP group,BS group and TP-SLN group were all effective in treating synovial blood flow and the bone erosion and there were no significant differences of ultrasonic and pathological scores among them(P>0.05).The ultrasonic scores of synovial blood flow(Z=-3.033,-2.842,-3.277all P<0.01)were lower than model group.The ultrasonic scores(Z=-2.948,-3.141,-3.210,all P<0.05)and pathological scores(Z=-2.216,-2.505,-2.505,all P<0.05)of bone erosion were also lower than model group.(6)There were significant correlations between ultrasonic and pathological scores of synovial inflammation and bone erosion(r=0.832 and 0.859 respectively,all P<0.001).(7)The positive rate of ultrasound examination was higher than that of pathology(?~2=5.657,all P<0.05).Conclusions:(1)TP,TP-SLN,and BS can inhibit the synovial inflammation and bone erosion in AIA rabbits.The treatment effect of TP-SLN is better than TP and no difference with BS.(2)The ultrasonic and pathological scores had a significant correlation in synovitis and bone erosion.Ultrasound can provide useful assessment of synovitis in early arthritis.