电离辐射致股骨头坏死早期病理特点和机制的研究

Earlier pathological character and mechanisms of irradiation necrosis on femoral head

目的观察单次大剂量射线引起大鼠股骨头坏死的早期病理改变，为放射性骨坏死特别是放射性股骨头坏死的早期诊断和防治研究提供依据。方法^137Csγ射线（30Gy）体外局部单侧单次照射大鼠股骨头，受照后2、6和12周取双侧股骨头HE染色，光镜观察病理改变；照后2周骨髓间充质干质细胞（bone marrow mesenchymal stem cells，BMSCs）分离培养，观察BMSCs增殖和集落形成能力；照后12周血管内灌注Microfill造影剂，采用微CT对股骨头毛细血管网进行三维重建和分析。结果^137Csγ射线局部照射后，受照侧股骨头软骨柱紊乱，骨细胞核皱缩、数量减少、空骨陷窝增多、骨小梁面积减少（P〈0.05）；受照侧股骨头毛细血管密度由未照侧的12.3％降至6.65％（P〈0.05）；BMSCs生长缓慢，集落形成率为10％，较对照组（21％）明显下降（P〈0.05）。结论30Gy单次局部照射后骨组织病理改变主要表现为空骨陷窝增加，照射后6周空骨陷窝率达30％可作为放射性股骨头坏死早期预诊断的指标之一。辐射致股骨头损伤甚至坏死除了射线对骨组织的损伤外，还与射线对骨髓BMSCs和毛细血管的损伤有关。

Objective To observe the earlier pathological character and mechanism of radiation osteoneerosis in femoral head, in order to provide evidences for the earlier diagnosis and prevention of radiation osteonecrosis of femoral head. Methods Single femoral head of rats were irradiated singly with 30 Gy of ^137 Cs γ-ray. The rats were executed after 2, 6 and 12 weeks, then the femurs were stained with HE and histopathological changes were observed by light microscope. The bone marrow mesenchymal stem cells （BMSCs） were cultured after 2 weeks and its proliferation and the colony formation were observed. The rats were endo- perfused with microfill contrast medium 12 weeks later, and the 3-dimensional structure of capillaries by Micro-CT was re-established to detect the pathological changes of capillaries after irradiation. Result The irradiated femur showed deranged chondrocyte, decreased osteocyte, shrinking nucleus, increased empty bone lacuna and reduced bone trabecula （P〈 0.05）. Micro-CT showed the discontinued small vessels and absence（6.65%） capillaries in irradiated femur were obviously less than those of the unirradiated （12.3%）（P〈0.001）. The proliferation of BMSCs was slowed, the number of colony in irradiated group （10%） was less than that of control （21%） （P〈0.001）. Conclusions The preliminary histopathological changes of osteoradionecrosis on femoral head could be increased the empty bone lacuna, and the bone lacuna above 30% was the sign of the earlier period of osteoradionecrosis. The osteonecrosis of femoral head induced by radiation is not only correlated to the damages to the bone, but also to the damages to BMSCs and capillaries.