表达脑源性神经营养因子的人多发性骨髓瘤小鼠模型的建立论文.docVIP

　　表达脑源性神经营养因子的人多发性骨髓瘤小鼠模型的建立论文 王雅丹，胡豫，张璐，黄靖，孙春艳 【摘要】 过去的研究证实脑源性神经营养因子（BDNF）在体外具有促进多发性骨髓瘤（MM）细胞增殖并诱导MM血管新生的能力。本研究探讨BDNF/TrkB途径是否为治疗MM的潜在靶点，并比较两种途径建立人MM NOD/SCID小鼠模型的优缺点，为深入探索治疗MM的新靶点奠定基础。选择糖尿病抵抗/重症联合免疫缺陷（NOD/SCID）小鼠，通过皮下注射或尾静脉注射人骨髓瘤细胞株RPMI8226建立两种异体移植动物模型。观察荷瘤后小鼠的生长状态.freell和（105±18）pg/ml。结论：本研究成功建立了两种高表达BDNF的MM荷瘤NOD/SCID小鼠模型，两种模型相互结合应用，为探索MM治疗的新靶点BDNF/TrkB提供了合适的动物模型。 【关键词】 多发性骨髓瘤 Establishment of Multiple Myeloma Mouse Models Expressing Brain Derived Neurotrophic Factor Abstract Previous studies have demonstrated the effects of brainderived neurotrophic factor (BDNF) on promoting proliferation of multiple myeloma (MM) cells and inducing angiogenesis in MM in vitro. This study ed to further explore an myeloma xenograft in animal models. The models of xenograft tumors munodeficiency (NOD/SCID) mice by subcutaneous or intravenous injection of human myeloma cell line RPMI8226. Mice onitored daily for life state, and the volume of subcutaneous tumors easured after inoculation. 3 a, human λ light chain and calcium level in serum of NOD/SCID inations ed to observe pathological features of tumors. Using floetry to observe the expression of human CD38+ cell in murine blood and bone marroal model shoors (5/5) and several pathological features of plasmacytomas. There levels, nor spread of human MM cells to murine bone marroal model had relative loors (4/7) but MM cells could engraft and proliferate in murine bone marroan λ light chain could be detected in serum as early as 3 abearing mice had high level of λ light chain and high calcium in serum and resorption of the murine bone. Furthermore, the concentrations of BDNF or groodels l and（105±18）pg/ml in plasma respectively at 9 al models a. Therefore, ts to explore novel therapeutic target (BDNF/TrkB) in MM have been set up successfully. Key ultiple myeloma; animal model; brain derived neurotrophic factor J Exp Hematol 2007; 15(5):967-972 表达脑源性神经营养因子的人多发性骨髓瘤小鼠模型的建立 我们的研究已经证实，脑源性神经营养因子（BDNF）与其高亲合力的受体TrkB结合后，具有诱导多发性骨髓瘤（