脑血栓候选新药磷脂酰丝氨酸脑靶向脂质体的实验研究

项目名称： 脑血栓候选新药磷脂酰丝氨酸脑靶向脂质体的实验研究

项目编号： No.30800360

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 张剑

作者单位： 绍兴文理学院

项目金额： 22万元

中文摘要： 脑血栓的治疗主要是抢救梗塞周边区潜在可挽救的缺血脑组织，防止继发性损害的产生。梗塞灶周边区脑组织的缺血损伤虽不足以引起细胞凋亡，但是足够激活细胞表面暴露的“#39135;我”凋亡信号磷脂酰丝氨酸（PS），引起小胶质细胞（MI）的识别和吞噬。虽然这些一过性呈现凋亡细胞特征的细胞只要不被临近的MI识别而吞噬，细胞的死亡状态就可能被逆转。因此本研究利用PS脑靶向脂质体作为携带药物进入脑内的特异性载体，竞争拮抗缺血损伤神经元表面一过性、可逆性表达的PS，阻断MI的吞噬作用，使损伤神经元有时间恢复活性；另一方面，通过MI吞噬PS后产生炎症调节性细胞因子前列腺素E2 (PGE2),抑制TNF-α31561;损伤性炎性因子的产生、促进IL-10等抗炎性细胞因子和神经保护因子的产生，发挥MI在脑缺血中的保护作用。为开发脑血栓候选新药PS脑靶向脂质体提供可靠的理论基础和药理学前期实验，为脑血栓疾病的急性期治疗提供崭新的思路。

中文关键词： 小胶质细胞；细胞凋亡；磷脂酰丝氨酸；脑靶向脂质体；脑血栓

英文摘要： The therapy of acute cerebral infarction is mainly that rescues ischemic penumbra and prevents the production of sequential injury. Although the ischemia damage of penumbra is insufficient to cause neuron apoptosis, but damage was enough to activate the apoptosis signal in cell surface that externalized phosphatidylserine (PS) meaning " to eat me ", and causes the recognition and phagocytosis by microglia. Although these cells have temporarily presented characteristic of apoptosis, but if they are not recognized and swallowed by microglia, The condition of cell apoptosis is possible to be reversed. Therefore using PS liposomes targeted for brain in this research, competitive antagonizes the invertable expression of PS in neuron surface of ischemia, blocks the phagocytosis of microglia, causes damaged neuron to have the time to restore activeness; On the other hand, microglia produces inflammation adjustment factor prostaglandin E2 (PGE2) induced by swallows PS, suppresses the productions of damage inflammatory factor TNF-αpromote production of nerve protection factor IL-10, displays the protective function of microglia in the brain ischemia. Provides the reliable rationale and the pharmacology earlier period experiment for the development of candidate new drug PS liposomes targeted to brain for cerebral thrombus, provides the new mentality for therapy of acute cerebral infarction.

英文关键词： microglia；neuron apoptosis；phosphatidylserine；liposomes targeted for brain；brain infarction