靶向肝脾巨噬细胞治疗血小板减少性紫癜的实验研究.DOCVIP

临床医学论文-靶向肝脾巨噬细胞治疗血小板减少性紫癜的实验研究 【摘要】? 本研究制备兔抗鼠血小板血清以建立SD大鼠免疫性血小板减少性紫癜（ITP）模型，使用明胶微粒装载二氯亚甲基二膦酸（Cl2MDP），并将药物导向模型的肝脾巨噬细胞内以杀伤巨噬细胞或降低其免疫活性，以期达到治疗ITP的目的。每24小时重复注射1次抗血小板血清150 μl，所建立的SD大鼠的ITP模型中，血小板计数于实验期间能维持在低于50×109/L的病理水平。用Cl2MDP明胶微粒进行巨噬细胞株RAW264.7的MTT试验及模型的实验性治疗，以治疗前后的血小板计数和出血时间作为疗效的观察指标。结果表明：Cl2MDP明胶微粒呈剂量依赖关系抑制体外培养的巨噬细胞的增殖并可迅速、有效地升高模型鼠血小板的数量，平均达180×109/L水平，并能维持血小板计数在生理范围内而不下降。此外，预先注射Cl2MDP明胶微粒的SD大鼠可避免抗血小板血清引起的血小板计数降低。结论：Cl2MDP明胶微粒静脉注射可以有效地提高SD大鼠ITP模型的血小板数量，达到避免发生出血的安全水平。这种靶向巨噬细胞的药物输送技术为ITP的治疗提供了一种新的治疗理念和方法，值得进一步深入研究。 【关键词】? 免疫性血小板减少性紫癜 二氯亚甲基二膦酸盐 明胶微粒 巨噬细胞 靶向治疗 ???? Experimental Study for? Thrombocytopenic Purpura Therapy by Targeting Macrophages in Liver and Spleen ?????? Abstract??? The study purpose was to? explore whether dichloromethylene diphosphonate (Cl2MDP)loaded gelatin particles can induce the depletion of macrophage in reticuloendothelial system of liver and spleen or can depress the immunity of macrophage in SD rat models of immune thrombocytopenic purpura (ITP) to treat the ITP rats.? New Zealand rabbits were immunized with platelets of SD rats to prepare rabbit antirat platelet serum, and the serum was intravenously injected into SD rats to produce the ITP model. In experimental ITP models, 150 μl of antiplatelet serum was intravenously injected into SD rats per 24 hours. The platelet counts maintained pathological level and were persistently less than 50×109/L in the models during experiment? process. The MTT test of macrophage RAW264.7?? was carried out? by means of? Cl2MDPloaded gelatin particles in vitro. After intravenous injection of a group dose of Cl2MDPgelatin particles, the platelet counts of the rats were measured at the time of 4 hours, 24 hours, 48 hours, 72 hours and 96 hours, respectively, and bleeding times were detected in 24 hours. The results showed that Cl2MDPloaded gelatin particles? increased the platelet counts of ITP models to mean of 180×109/L, a physiological level in 24 hours after injection, and? kept this platelet le