中文摘要：

目的观察唑来膦酸（zA）对破骨细胞（OC）分化、增殖和骨髓微环境的影响，探讨ZA抗辐射（IR）后小鼠骨量丢失的机制。方法50只雄性BALB／c小鼠经6．0Gy^60Coγ射线一次性全身辐射后，随机分成辐射组10只，高、中、低剂量治疗组30只和骨髓输注组10只。治疗组分别按0．00025、0．00050、0．00100mg／g进行尾静脉注射ZA，骨髓输注组4h内尾静脉回输异体骨髓细胞2×10^6个。4周后应用小动物成像仪测定小鼠骨密度，流式细胞术检测骨髓中破骨原始细胞（CD34＋CD115＋细胞）、破骨前体细胞[CD34＋CD115＋核因子-κB受体活化因子配体（RANKL）＋细胞]及其活化细胞[CD34＋CD115＋RNAKL＋CXC趋化因子受体4（CXCR4）＋细胞]的百分比，骨及骨髓病理分析骨小梁及破骨前体细胞的变化，小动物五分类血细胞分析仪检测外周血破骨前体细胞（单核细胞）的百分比及绝对值。流式微球阵列（CBA）和酶联免疫吸附试验（ELISA）法检测血清中OC活化相关因子的含量。结果辐射组，低、中、高剂量治疗组，骨髓输注组小鼠骨密度分别为（0．51±0．06）、（1．26±0．17）、（2．24±0．29）、（1．27±0．20）、（2．52±0．23）r／cm^3。辐射组显著低于各治疗组和骨髓输注组（P均为0．000），中剂量治疗组高于低剂量治疗组和高剂量治疗组（P=0．000、0．942），与骨髓输注组接近（P=0．004）。中剂量治疗组CD34＋CD115＋细胞、CD34＋CD115＋RANKL＋细胞、CD34＋CD115＋RANKL＋CXCR4＋细胞的百分比分别为（4．09±0．97）％、（4．11±1．64）％、（18．71±6．23）％，显著低于辐射组[（7．19±1．11）％、（9．01±4．06）％、（40．16±10．31）％]，差异有统计学意义（P=0．000、0．000、0．000）。与骨髓输注组[（10．14±2．13）％、（2．86±0．82）％、（11．86±3．39）％]接近，差异有统计学意义（P=0．000、0．241?

英文摘要：

Objective To study the mechanism of how zoledronic acid （ZA） inhibit the bone loss in mice which were suffered total ionizing radiation （ IR）, we would discuss through three aspects including osteoclast （OC） proliferation, OC differentiation and the bone marrow mirco - environment. Methods 50 male BALB/c mice suffered one - time 6. 0 dose radiation were randomly divided into 5 groups, 10 in radiation group, 30 in low, middle, high treatment group, 10 in bone marrow group. Low, middle, high treatment groups were each injected with 0. 000 25, 0. 000 50, 0. 001 00 mg/g ZA through caudal vein. Bone marrow group were injected with 2 × 10^6 allograft bone marrow ceils in 4 hours. 4 weeks later, detect bone mineral density by small animal imaging measurement. Count the percentage of osteoclast primitive ceils （ CD34 ＋ CD115 ＋ ）, osteoclast precursor cells [ CD34 ＋ CD115 ＋ receptor activator of nuclear factor κB lig- and （RANKL）＋] and its activate cells [ CD34＋ CD115＋ RANKL± CXC chemokine receptor 4 （CXCR4） ＋ ] in bone marrow by flow cytometry. Analyzed bone trabecular and osteoclast precursor cells by bone marrow pathology. Detected the percentage and absolute value of blood cells and osteoclast precursor cells by mall animals 5 classification blood cell analyzer. Assess the level of cytokines in serum related with OC activation by cytometric beads array （CBA） and enzyme -linked immuno sorbent assay （ELISA） kits. Results The bone mineral density of mice in radiation group, low treatment group, middle treatment group, high treatment group and bone marrow group were correspondingly （0.51 ± 0.06）, （1.26 ± 0. 17）, （2. 24 ±0. 29）, （ 1.27 ±0.20）, （2. 52 ±0. 23） g/cm3. The bone mineral density of mice in radiation group were lower than others in four groups （ P = 0. 000）. The bone mineral density of mice in mid- dle treatment group were higher than low treatment group and high treatment group （P = 0. 000, P = 0. 942） and got close to bone marro