目的:评价超声引导下关节腔内注射雷公藤甲素固体脂质纳米粒(TP-SLN)治疗兔抗原诱导性关节炎(AIA)的疗效。材料和方法:33只AIA新西兰兔的膝关节关节内注射雷公藤甲素(TP:n=7),TP-SLN(n=7),倍他米松(BS:n=7)和二甲基亚砜(DMSO:n=6)。其余六只兔子未处理作为对照组。干预组的注射治疗在最后一次免疫后1周开始,以避免在后期诱导中不可逆的关节损伤。根据滑膜炎评估关节的超声评分,滑膜血流和骨侵蚀。同时,确定超声评分与病理评分的相关性。结合超声评分判断各组的疗效和副作用,病理评分,行为,食欲,体重,接头直径,皮肤温度和生化检查。结果:1)与对照组相比,TP的膝关节直径,TP-SLN和BS组在关节内注射后1周开始降低(p<0.01)。2)除DMSO组外,与对照组相比,干预措施治疗滑膜炎有效,TP-SLN和BS是最好的。TP组滑膜炎的超声和病理评分均低于模型组(Z=-2.726和-2.530,p<0.05)。超声评分在BS组和TP-SLN组之间差异显著(Z=-2.17和-2.360,p<0.05)和病理评分(Z分别为-2.687和-2.082,p<0.05)。3)与对照组相比,TP,BS和TP-SLN均可有效治疗滑膜血流和骨侵蚀,超声和病理评分之间无明显差异(p>0.05)。滑膜血流的超声评分(Z=-3.033,-2.842,-3.277,p<0.01)低于对照组。骨侵蚀的超声评分(Z=-2.948,-3.141,-3.210,p<0.01)和病理评分(Z=-2.216,-2.505,-2.505,p<0.05)也低于模型组。4)滑膜炎症和骨侵蚀的超声与病理评分之间存在显着相关性(r分别为0.832和0.859,p<0.001)。结论:TP-SLN治疗关节炎的疗效优于TP,但是BS和TP-SLN之间没有区别。因此,TP-SLN有可能替代BS治疗类风湿关节炎。滑膜炎和骨侵蚀的超声和病理评分显示出明显的相关性。超声可以提供早期关节炎滑膜炎的有用评估。
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. Material and Methods: Knee joints of 33 New Zealand rabbits with AIA were injected intra-articularly with triptolide (TP: n = 7), TP-SLN (n = 7), betamethasone (BS: n = 7) and dimethyl sulfoxide (DMSO: n = 6). The remaining six rabbits were untreated as the control group. The injection therapy in intervention groups was initiated 1 week after the last immunization in order to avoid irreversible joint damage in the later induction. The ultrasonic scores of the joints were assessed based on synovitis, synovial blood flow and bone erosion. Meanwhile, the correlations of ultrasonic scores and pathological scores were determined. The efficacy and side effects of each group were determined by combining ultrasonic scores, pathological scores, behavior, appetite, weight, joint diameter, skin temperature and biochemical examination. Results: 1) Compared with the control group, the diameters of knee joints of the TP, TP-SLN and BS groups began to reduce 1 week after intra-articular injection (p < 0.01). 2) With the exception of the DMSO group, the interventions were effective in treating synovitis compared with the control group, with TP-SLN and BS being the best. The ultrasonic and pathological scores in synovitis of the TP group were lower than that of model group (Z = -2.726 and -2.530, p < 0.05). The ultrasonic scores differed significantly between BS group and TP-SLN group (Z = -2.17 and -2.360, respectively, p < 0.05) and pathological scores (Z = -2.687 and -2.082, respectively, p < 0.05). 3) Compared with the control group, the TP, BS and TP-SLN were all effective in treating synovial blood flow and 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, -3.277, p < 0.01) were lower than in the controls. The ultrasonic scores (Z = -2.948, -3.141, -3.210, p < 0.01) and pathological scores (Z = -2.216, -2.505, -2.505, p < 0.05) of bone erosion were also lower than in the model group.4) There were significant correlations between the ultrasonic and pathological scores of synovial inflammation and bone erosion (r = 0.832 and 0.859 respectively, p < 0.001). Conclusions: The therapeutic effect of TP-SLN on arthritis is better than that of TP, but there is no difference between BS and TP-SLN. Therefore, TP-SLN may be used as an alternative to BS in the treatment of rheumatoid arthritis in the future. The ultrasonic and pathological scores showed significant correlation in synovitis and bone erosion. Ultrasound can provide a useful assessment of synovitis in early arthritis.