腔内注射雷公藤甲素纳米材料治疗抗原诱导的兔关节炎的实验研究

目的探讨关节腔内注射雷公藤甲素纳米材料(TPNA)对抗原诱导的兔关节炎的治疗效果。方法新西兰大白兔27只,采用完全随机区组设计法分配为4组,建立抗原诱导的关节炎模型后,TPNA组、雷公藤甲素组(TP组)和倍他米松组(BS组)分别于超声引导下向关节腔内注射TPNA、单纯TP、倍他米松,每组7只;对照组(6只)仅穿刺但不注射任何药物。观察关节肿胀度,滑膜炎及骨破坏等病理变化。统计学方法采用t检验、重复测量的方差分析、Mann-Whitney U检验、Kruskal-Wallis检验。结果①末次免疫1周后即治疗前TPNA组、TP组、BS组和对照组兔膝关节直径大小分别为(2.02±0.08)cm,(2.08±0.06)cm,(2.10±0.06)cm和(2.18±0.07)cm,在给药1周后上述各组膝关节直径分别为(1.85±0.06)cm、(1.89±0.07)cm、(1.93±0.08)cm和(2.15±0.08)cm,各个给药组关节肿胀均见明显改善。随着治疗的进行,TP组、TPNA组和BS组兔膝关节直径逐渐减小(F=58.83,P<0.01;F=53.78,P<0.01;F=68.24,P<0.01),而且TP组、TPNA组和BS组兔膝关节直径明显小于对照组,差异有统计学意义(F=63.83,P<0.01;F=71.94,P<0.01;F=140.79,P<0.01)。②TP组滑膜炎病理评分较对照组低(Z=-2.082,P<0.05),以轻度滑膜炎为主,而TPNA组和BS组滑膜病理评分比TP组低(Z=-2.082,P<0.05;Z=-2.687,P<0.05),大多无滑膜炎表现,BS组与TPNA组间差异无统计学意义(Z=-1.000,P>0.05)。③TPNA组、TP组以及BS组骨质破坏的病理评分均比对照组减轻(Z=-2.505,P<0.05;Z=-2.216,P<0.05;Z=-2.505,P<0.05),TPNA组、TP组以及BS组间差异无统计学意义(χ2=0.588,P>0.05)。结论关节腔内注射TPNA可以缓解关节肿胀,减轻滑膜炎,延缓骨破坏的形成。其效果与糖皮质激素相当,好于单纯TP。关节腔内注射TPNA有望成为治疗关节炎的有效手段。

An experimental study on intra-articular injection of triptolide nanomaterials for the treatment of rabbit arthritis

Objective To explore the therapeutic effect of intra-articular injection of triptolide nanomaterials on rabbit antigen-induced knee arthritis.Methods Twenty-seven New Zealand white rabbits were randomly divided into 4 groups.After antigen-induced arthritis(AIA)model were induced,the knee joints of triptolide nanomaterials(TPNA)group,triptolide(TP)group and betamethasone(BS)group were injected intra-articularly under ultrasound guidance with triptolide nanomaterials,triptolide and betamethasone respectively,7 rabbits in each group.And the other 6 rabbits were punctured but not injected with any drugs as the control group.The pathological changes of joint swelling,synovitis and bone erosion were examined.Student's test,repeated measure data of analysis of variance(ANOVA),Mann-Whitney U test and Kruskal-Wallis test were used for statistical analysis.Results①Before treatment,the knee joint diameters of the TPNA group,TP group,BS group and control group were(2.02±0.08)cm,(2.08±0.06)cm,(2.10±0.06)cm and(2.18±0.07)cm,respectively.After one week of administration,the knee joint diameters of the above groups were(1.85±0.06)cm,(1.89±0.07)cm,(1.93±0.08)cm and(2.15±0.08)cm,respectively.Knee joint swelling was significantly reduced in each treated group after a week of intra-articular injection.With the extension of treatment,the diameter of rabbit knee joints in each experimental group gradually decreased gradually(F=58.83,P<0.01;F=53.78,P<0.01;F=68.24,P<0.01),and the diameter of rabbit knee joints in the TP group,TPNA group and BS group was significantly smaller than that of the control group(F=63.83,P<0.01;F=71.94,P<0.01;F=140.79,P<0.01).②The synovitis score of TP group was lower than that of the control group(Z=-2.082,P<0.05),which was mainly mild synovitis.While the synovitis scores of TPNA group and BS group were lower than that of TP group(Z=-2.082,P<0.05;Z=-2.687,P<0.05),most of which were free from synovitis.There was no statistical significant difference between BS group and TPNA group(Z=-1.000,P>0.05).③The pathological scores of bone destruction in the TPNA group,TP group and BS group were all reduced compared with the control group(Z=-2.505,P<0.05;Z=-2.216,P<0.05;Z=-2.505,P<0.05).There was no statistical significant difference between the TPNA group,TP group and BS group(χ2=0.588,P>0.05).Conclusion Intra-articular injection of triptolide nanomaterials can relieve joint swelling,reduce synovitis,and delay bone erosion.Its effect is similiar to glucocorticoid,better than simple triptolide.Triptolide nanomaterials have the potential to be an effective drug for arthritis by intra-articular injection.