| Part one: Study on the rat model of knee tophi induced by repeated intra-articular injection of monosodium urate under ultrasound guidanceObjective:In this study,the tophi model of rat knee joint was induced by repeated intra-articular injection of monosodium urate under ultrasound guidance,and then high-frequency ultrasound with firefly technology was used to detect the tophi in the knee joint.The mechanism of tophi damage to the knee cartilage of rats was studied from the positive direction.Methods:Forty SD rats were randomly divided into four groups.The control group was injected PBS solution 0.1ml every 3 days under ultrasound guidance.The monosodium urate group was injected sodium urate solution0.1ml every 3 days under ultrasound guidance.The monosodium urate combined with celecoxib group was injected monosodium urate solution 0.1ml every 3 days under ultrasound guidance,and celecoxib(20mg / kg)was taken orally 6 hours later.The celecoxib group,0.1ml PBS solution was injected into knee joint cavity every 3 days under ultrasound guidance,and celecoxib(20mg /kg)was taken orally 6 hours later.High-frequency ultrasound combined with firefly technology was used to detect the formation of tophi in rat knee joint.HE staining was used to observe the inflammatory reaction of synovial tissue.Safranin O-solid green staining was used to observe the cartilage destruction.Tartrate resistant acid phosphatase(TRAP)staining was used to observe the distribution of TRAP positive cells in subchondral bone.ELISA was used to detect the expression levels of IL-1 β,IL-6 and TNF-α in serum of SD rats.T-test was used to compare the data between group,and one-way ANOVA was used to compare the data between groups.Results:Five months later,by high-frequency ultrasound combined with firefly technology detection,tophi crystal deposition could be found in the monosodium urate group,while a small amount of tophi crystal deposition could be found in the monosodium urate combining with celecoxib group,and no tophi deposition was found in the control group and celecoxib group.The circumference of the knee joint in the monosodium urate group was significantly larger than that in other groups(P<0.05).There were significant differences between monosodium urate group and other groups.HE staining in the monosodium urate group indicated synovial tissue inflammation.The results showed that the inflammatory reaction was obvious,with a large number of inflammatory cells infiltration.Safranin O-solid green staining showed that the cartilage and bone erosion of rats in monosodium urate group was obvious,and celecoxib could reduce the inflammatory reaction caused by repeated joint injection of monosodium urate,and reduce the bone erosion of knee joint.Tartrate resistant acid phosphatase(TRAP)staining showed that TRAP positive cells could be found in subchondral bone of rats in monosodium urate group.The levels of IL-1β,IL-6 and TNF-α in serum of SD rats were detected by ELISA.There were significant differences between monosodium urate group and other groups(P<0.05).Conclusions:Repeated injection of monosodium urate into the knee joint cavity of rats under ultrasound guidance can induce the model of knee tophi.Tophi can cause invasive bone damage to the knee joint,and it is easy to deposit on the injured articular cartilage surface.Part two: Efficacy of arthroscopic debridement combined with febuxostat in the treatment of knee tophi.Objective:To further verify the destructive effect of tophi on knee joint,the protective effect of tophi removal on knee function was studied in reverse direction,which provided further theoretical basis for arthroscopy for the treatment of tophi.Methods:According to the principle of randomized,controlled and non blind clinical trials,60 patients with knee tophi were divided into two groups: knee arthroscopy treatment group(30 cases)and control group(30 cases)according to the distribution principle of minimum disequilibrium index.They were followed up for one year,and were recorded before treatment(M0),3 months(M3),6 months(M6),9 months(M9)and 12 months(M12)respectively.The results of laboratory examination,ultrasound examination and clinical examination were performed and evaluated.The clinical observation indexes included visual analogue score(VAS),Lysholm score and range of motion of knee joint.The changes of knee tophi were observed by high-frequency ultrasound combined with firefly technology.The laboratory indicators include the detection of serum uric acid(UA),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP)levels.The enzyme linked immunosorbent assay(ELISA)was used to detect the expression levels of interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in serum.The clinical efficacy was evaluated by knee flexion and extension range of motion,Lysholm score and VAS score.The operation and drug-related complications were observed and recorded.T-test was used to compare the data between group,and one-way ANOVA was used to compare the data between groups.Results:By compared the serum uric acid,erythrocyte sedimentation rate,C-reactive protein,IL-1β,IL-6 and TNF-α levels,the difference between the two groups was statistically significant(P<0.05).The VAS score of knee joint between the two groups was statistically significant(P<0.05),and VAS score gradually decreased;The Lysholm score of knee joint between the two groups was statistically significant(P<0.05),and Lysholm score increased gradually.The difference of knee flexion and extension range of motion between the two groups was statistically significant(P<0.05),and the flexion and extension range of motion increased gradually.High-frequency ultrasound combined with firefly technology detected the changes of knee tophi,the treatment group of knee tophi disappeared significantly than the control group,and the knee tophi gradually disappeared.During the one-year follow-up,the attack rate of acute gout was 3.33% in the treatment group and 30% in the control group,with significant difference between the two groups(P<0.05).During the treatment,there was no significant difference in the incidence of drug-related complications between the two groups(P<0.05).Conclusions:High-frequency ultrasound combined with firefly technology can be used to observe the changes of knee tophi.Febuxostat alone has limited effect on the treatment of knee tophi.The short-term effect of arthroscopy combined with febuxostat in the treatment of knee tophi is better than that of febuxostat. |
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