【摘要】 目的 探讨FKBP51·PHLPPL·AKT模块在大鼠脑缺血/再灌注(I/R)损伤中的作用及其机制。方法采用Pulsinelli-Briorley法制作大鼠全脑缺血损伤模型。将大鼠随机分成假手术组、I/R(分8个时间点)组。采用免疫印迹法测定PHLPPL(PH domain and leucine rich repeat protein phosphatases,PH结构域并且富含亮氨酸重复基序的丝/苏氨酸蛋白磷酸酶)蛋白表达,免疫共沉淀法测定FKBP51(FK506 binding protein 5,FK506连接蛋白5)、PHLPPL及Akt(PKB,蛋白激酶B)结合情况。结果 与假手术组相比,I/R组在海马组织PHLPPL表达水平差异无统计学意义(P>0.05)。FKBP51、PHLPPL及Akt可共沉淀形成模块;I/R组中Ir 6h亚组与假手术组相比,模块结合具有统计学意义(P<0.05),且模块结合于Ir 6h达到高峰。结论 PHLPPL表达于海马且PHLPPL表达不受缺血复灌时间影响,但FKBP51·PHLPPL·Akt模块形成具有时间依赖性,推测FKBP51·PHLPPL·Akt模块的形成可能参与了脑缺血再灌注损伤机制。更多还原

【Abstract】 Objective To explore the mechanism and effect of the FKBP51·PHLPPL·AKT module on global brain ischemia/reperfusion(I/R) induced neuronal death in rat hippocampus.Methods Global cerebral ischemia was induced by the method of Pulsinelli-Briorley(four-vessel occlusion).The SD rats were randomly divided into two groups:the sham group(Sham),the I/R group(8 differernt points or subgroups).Results Immunoblotting showed that the level of PHLPPL expression in the rat hippocampus had no significant changes noticed in sham-controlled rats at different time points.FKBP51(FK506 binding protein 5),PHLPPL(PH domain and Leucine rich repeat Protein Phosphatases) and Akt(PKB) could be co-precipitation,which could form a module.The data showed that the FKBP51·PHLPPL·AKT module elevated gradually after ischemia/reperfusion,and peaked at 6 h of reperfusion,then fell.Conclusion The FKBP51·PHLPPL·AKT signal module plays an important role in cerebral ischemia injury.Thereby,we speculate that the FKBP51·PHLPPL·AKT signal module may be involved in the ischemia injury,and becomes one of the mechanisms of cerebral ischemic injury.更多还原