腺苷受体A2A抑制剂ZM241385对骨折愈合生物力学的影响

目的 评估腺苷受体A2A抑制剂ZM241385对骨折愈合生物力学的影响。方法 采用温敏水凝胶聚乙交酯丙交酯（PLGA）-聚乙二醇（PEG）-聚乙交酯丙交酯（PLGA）溶解ZM241385制备缓释系统。取20只大鼠随机分为腺苷受体A2A抑制剂组与对照组，每组10只。制备大鼠股骨干骨折模型，造模时骨折局部应用ZM241385缓释系统，造模后每24 h骨折局部im相应药物，持续7 d。造模后第14、28天对大鼠骨折局部进行micro-CT扫描，测量骨折局部总体积、骨体积、骨痂体积。通过Ansys Workbench 2017软件进行仿真分析，对大鼠骨折局部施加轴向以及旋转应力评估骨折生物力学强度。结果 腺苷受体A2A抑制剂组大鼠造模后14 d总体积、骨体积、骨痂体积均显著低于对照组，差异有统计学意义（P＜0.05、0.01）。造模后28 d，腺苷受体A2A抑制剂组大鼠总体积、骨痂体积均超过对照组，差异具有统计学意义（P＜0.01），骨体积无统计学差异。当轴向应力为1、5、10 N或者旋转应力为0.5 N·m时，腺苷受体A2A抑制剂组造模后14、28 d最大应力、最大应变、平均位移均显著高于对照组，差异具有统计学意义（P＜0.001）。结论 腺苷受体A2A抑制剂明显抑制骨愈合，降低骨折局部轴向和旋转的力学强度，腺苷受体A2A可能是发生二次骨折或骨不连的关键受体。

Effects of adenosine receptor A2A inhibitor ZM241385 on biomechanical strength of fracture healing

Objective To evaluate the effects of adenosine receptor A2A inhibitor on biomechanics strength of fracture healing. Methods PLGA-PEG-PLGA was used to dissolve receptor inhibitor to make drug delivery system. 20 rats were randomly divided into inhibitor group and control group with 10 rats in each group. The femoral shaft fracture rat model was made, and the drug release system was applied to the fracture site. Rats were received the corresponding drugs every 24h during seven days after modeling by fracture site injection. On the 14th and 28th day after modeling, micro CT scanning was performed to measure the total volume, bone volume and callus volume. Through the simulation analysis of ANASYS workbench 2017 software, the axial and rotational stresses were applied to evaluate the biomechanical strength of the fracture. Results The total fracture volume, bone volume and callus volume of the inhibitor group were significantly lower than those of the control group at 14 d after model (P < 0.05 and 0.01). At 28 d after modeling, the total volume and callus volume in adenosine receptor A2A inhibitor group were higher than those in control group, the differences were statistically significant (P < 0.05), but there was no significant difference in bone volume. When the axial stress was 1, 5, 10 N or the rotational stress was 0.5 N·m, the maximum stress, maximum strain and average displacement of the inhibitor group were significantly higher than those of the control group at 14 and 28 d after model (P < 0.001). Conclusion adenosine receptor A2A inhibitor inhibits bone healing and is closely related to bone biomechanical strength. After inhibiting the receptor, the axial and rotational mechanical strength of fracture decreased significantly, and secondary fracture or nonunion were prone to occur