树鼩脑缺血半暗区PAF受体介导的微环境改变及GB保护机制的探讨  

PAF Receptor Mediating the Microenvironment Alteration in Ischemic Penumbra and the Neuroprotective Effect of Gingklide B After Cerebral Ischemia in Tree Shrews

作　　者：李树清[1] 杨丽君[1] 张利能[1] 孟强[1] 张颖[1] 

机构地区：[1]昆明医学院基础医学院病理生理教研室,云南昆明650031

出　　处：《中国微循环》2005年第5期301-304,310,共5页Journal of Chinese Microcirculation

基　　金：国家教育部博士点专项基金;云南省自然科学基金资助项目(编号:99C0065M)

摘　　要：目的研究树鼩血栓性脑缺血时,血小板活化因子(PAF)受体活化介导的缺血半暗区微环境改变,并探讨PAF受体拮抗剂—银杏内酯B(ginkgolide,GB)的神经保护机制。方法采用光化学诱导树鼩血栓性局部性脑缺血模型,用3H?PAF放射免疫标记法检测缺血区微环境脑细胞PAF受体亲合性(Kd值)和结合特性(Bm ax值)的变化;用密度梯度法及原子吸收分光法分别测定缺血微环境水含量及Na+、Ca2+含量,并于光化学反应后6 h静注GB(5 mg/Kg),观察其对脑血栓形成后24 h时缺血微环境的改善效应。结果树鼩脑血栓形成后缺血半暗区微环境的改变以24 h为著,脑细胞膜高亲和性、低亲和性PAF受体的Kd值及Bm ax值明显降低,其中Kd1及Bm ax1分别为(0.611±0.9)nM和(419.4±72.6)fmol.mg-1蛋白,Kd2及Bm ax2分别为(4.08±0.5)nM和(676.8±98.66)fmol.mg-1蛋白(与对照组相比P<0.01);GB可促使缺血微环境脑细胞PAF受体Kd及Bm ax的恢复,并具有改善局部脑水肿和缓解Ca2+超载(P均<0.01)。结论PAF受体活化在介导缺血半暗区微环境改变中具有重要作用,GB可改善缺血半暗区微环境和逆转PAF受体活化介导的神经元泵功能障碍。Objective To study the platelet activating factor （PAF） receptor mediating the microenvirenment alteration in ischemic penumbra and to explore the neurepretective mechanisms of PAF receptor antagonist （ginkgolide B, GB） after cerebral thrombosis in tree shrews. Methods Thrombotic cerebral ischemia induced by photochemical reaction in tree shrews and the affinity （Kd） and binding sites （Bmax） of PAF receptor （^3H-labelled PAF assay ） and the changes of sodium （ Na^＋ ）, calcium（ Ca^2＋ ） and water content （ by specific gravimetric method ） were observed in the microenvirenment of ischemic penumbra. The animals were geven with GB 5mg. kg^-1 at 6h and the effects of improving ischemic microenvirenment were investigated at 24h after cerebral thrombosis. Results Two different affinities PAF receptor binding sites on the brain cell membrane within the microenvirenment of ischemic penumbra decreased significantly（ Kd1 and Bmax1： 0.611 ± 0.9 nM and 419.4 ± 72.6 fmol. mg^-1 protein, respectively, and Kd2 and Bmax2： 4.08 ± 0.5 nM and 676.8 ±98.66 fmol. mg^-1 protein, respectively）, especially at 24h （P 〈 0.01） after cerebral thrombosis. GB changed Kd and Bmax of PAF receptor of the call, and improved local cerebral edema and inhibited Ca^2 ＋ overload ischemic brain cells. Conclusion PAF receptor activation may play an important rele in the changes of microcnvirenment in ischemic penumbra and GB exerts neuroprotective effect by blockiag PAF receptor and improving the pump function of neurons.

关 键 词：脑缺血 微环境 血小板活化因子受体 半暗区 银杏内酯 树鼩 

分 类 号：R365[医药卫生—病理学] R743.33[医药卫生—基础医学]