^188Re-HEDP对体外成骨细胞增殖及细胞周期的影响  

Effect of ^188Re-HEDP on the osteoblasts： proliferation, differentiation and apoptosis

作　　者：程爱萍[1] 陈绍亮[1] 王洪复[2] 金慰芳[2] 高建军[2] 许长德 

机构地区：[1]复旦大学附属中山医院核医学科,上海200032 [2]复旦大学放射医学研究所骨代谢室 [3]上海市第五人民医院核医学科

出　　处：《中华核医学杂志》2008年第2期130-133,共4页Chinese Journal of Nuclear Medicine

摘　　要：目的观察不同剂量^188Re-羟基亚乙基二膦酸盐（HEDP）近距离作用对成骨细胞增殖和细胞周期的影响。方法在体外培养的成骨细胞中加入不同放射性浓度（0，1．85，9．61，48．00，240．50，462．50，832．50和1110．00kBq／m1）^188Re-HEDP，继续培养24h后检测细胞的放射性计数，了解成骨细胞摄取^188Re-HEDP的能力。用四甲基偶氮唑蓝（MTT）法检测成骨细胞增殖能力。测定细胞碱性磷酸酶（ALP）活性，以明确成骨细胞分化功能。采用流式细胞仪检测细胞周期变化。结果成骨细胞摄取^188Re-HEDP的能力较强，^188Re-HEDP≤1110．00kBq／ml时未观察到结合平台期。受^188Re-HEDP刺激后成骨细胞生长增殖旺盛、分化加强，成骨细胞存活率为（113．67±3．22）％-（122．00±6．58）％，ALP值为（0．42±0．02）-（0．50±0．05）U／L；^188Re-HEDP〉133．30MBq／ml时成骨细胞凋亡率增加[（6．26±0．09）％]并随剂量增大。^188Re-HEDP作用后处于合成期的成骨细胞百分率明显增加，为（22．32±2．31）％-（35．58±5．18）％。结论^188Re-HEDP可能刺激成骨细胞增殖和分化，使合成期的细胞百分率增高.^188Re-HEDP超过33．30MBq／ml时引起成骨细胞凋亡，且凋亡率与其放射性浓度呈正相关。Objective Radionuclide has been used in the treatment of bone metastasis in the last few decades but its effect-on osteoblasts is unclear. The aim of this work was to investigate the effects of different irradiation doses of ^188Re-hydroxyethylidenediphosphonate （HEDP） on the proliferation, differentiation and apoptosis of osteoblasts. Methods Osteoblasts from SD rats were cultured in vitro. The growing osteoblasts at the fifth generation were irradiated by ^188Re-HEDP at different doses （0,1.85,9.61,48.00, 240.50,462.50,832.50 and 1110.00 kBq/ml ）. The proliferation of osteoblasts was determined by its functional capability and growth characteristics , which were detected by uptake of ^188Re-HEDP using T counter and by the method of 3-（4,5-dimethyhhiazol-2-yl）-2,5-diphenylte-trazolium bromide （MTT） respectively. The differentiation and apoptosis of osteoblasts were examined by alkaline phosphatase （ALP） and flow cytometry respectively. Results The proliferation and differentiation of osteoblasts were enhanced after ^188Re-HEDP irradiation. The S period in cell cycle was augmented. The survival rate of osteoblasts was （113.67 ±3.22）% ;（122.00 ±6.58）%, the ALP was （0.42 ±0.02）; （0.50 ±0.05） U/L. The up- take of ^188Re-HEDP by osteoblasts did not reach equilibrium when the dose is less than 1110.00 kBq/ml. The apoptosis of osteoblasts occurred [ apoptosis rate ≥ （6.26 ＋ 0.09）% ] when ^188Re-HEDP dose was equal to or greater than 33.30 MBq/ml. The apoptosis rate was positively correlated with the ^188Re-HEDP activity concentration. Conclusions ,as Re-HEDP played the role in enhancing the proliferation and differentiation of osteoblasts when its irradiation dose was less or equal to 1110.00 kBq/ml. When the ^188Re-HEDP dose was equal to or greater than 33.30 MBq/ml, apoptosis of osteoblasts would occur.

关 键 词：成骨细胞 细胞分裂 细胞周期 体外研究 放射疗法 铼 HEDP 大鼠 

分 类 号：R686[医药卫生—骨科学]