目的研究地塞米松(Dex)高分子前药(P-Dex)对佐剂性关节炎(AIA)大鼠的疗效及其组织分布。方法于大鼠后足跖皮内注射完全弗氏佐剂建立关节炎大鼠模型,模型大鼠随机分为对照组、实验组和模型组,设健康大鼠空白组(均n=6)。对照组给予地塞米松磷酸钠(Dsp),试验组给予P-Dex,模型组与空白组给予生理盐水。建模前和建模后每3 d测定后肢踝关节直径和足掌厚度,给药后14 d取踝关节组织HE染色评价P-Dex对大鼠关节炎的治疗作用;超高效液相色谱-质谱串联法测定给药后不同时间点模型大鼠血浆、心、肝、脾、肺、肾及踝关节组织中Dex浓度,用DAS 2.0软件计算其药动学和组织分布参数。以踝关节对P-Dex和Dsp的相对摄取率及P-Dex对踝关节靶向效率为炎性关节靶向性评价指标对P-Dex靶向炎性关节特性进行评价。结果试验组给药后8 d踝关节直径及足掌厚度变化值明显小于对照组和模型组(P<0.05);试验组滑膜增生、软骨损坏较对照组和模型组轻,接近空白组。实验组PDex血浆t_(1/2)为32 h,血浆CL为(0.81±0.01)×10~(-4) L·h~(-1)·kg~(-1),AUC_(0-∞)为(3 135 973±1 932)ng·L~(-1)·h,是对照组Dsp的350倍。P-Dex主要分布在血浆、脾和肝中,游离Dex在踝关节组织中浓度最高。踝关节组织中P-Dex相对于Dsp的相对摄取率为1.22;Dsp和P-Dex靶向踝关节效率分别为9%和82%。结论 P-Dex具有较Dsp更为持久的抑制炎症作用,能够靶向于踝关节炎症部位,并在炎症部位选择性释放Dex。 Objective To study the therapeutic effect and tissue distribution of dexamethasone (P-Dex) on adjuvant arthritis (AIA) in rats. Methods The rat model of arthritis was established by intradermal injection of complete Freund’s adjuvant into the hindfoot of rats. The model rats were randomly divided into control group, experimental group and model group, and blank control group (all n = 6). The control group was given dexamethasone sodium phosphate (Dsp), the experimental group was given P-Dex, the model group and the blank group were given normal saline. The ankle joint diameter and calyx thickness of the hind limb were measured every 3 days before and after modeling. HE staining of the ankle joint tissue was performed 14 days after administration to evaluate the therapeutic effect of P-Dex on the arthritis in rats. Ultra performance liquid chromatography- The concentrations of Dex in the plasma, heart, liver, spleen, lung, kidney and ankle joints of the model rats at different time points after administration were determined by MS / MS. The pharmacokinetic and tissue distribution parameters were calculated by DAS 2.0 software. The P-Dex-targeted inflammatory joint characteristics were evaluated using the relative uptake rates of P-Dex and Dsp in the ankle joint and the targeting efficiency of P-Dex to the ankle joint as indicators of inflammatory joint targeting. Results The changes of ankle diameter and calyx thickness on the 8th day after administration in the experimental group were significantly smaller than those in the control group and the model group (P <0.05). The synovial hyperplasia and cartilage damage in the experimental group were lighter than those in the control group and model group, and were close to the blank group. In the experimental group, the plasma t_ (1/2) of PDex was 32 h and the plasma CL was (0.81 ± 0.01) × 10 ~ (-4) L · h -1 · kg -1. The AUC_ (0 ~ ∞ ) Was (3 135 973 ± 1 932) ng · L ~ (-1) · h, which was 350 times of that of the control group. P-Dex is mainly distributed in plasma, spleen and liver, and free Dex has the highest concentration in ankle joint tissues. The relative uptake of P-Dex relative to Dsp in the ankle joint was 1.22; the targeted ankle efficiencies of Dsp and P-Dex were 9% and 82%, respectively. Conclusion P-Dex has a more prolonged anti-inflammatory effect than Dsp, targeting the site of ankle arthritis and selectively releasing Dex at the site of inflammation.