缺血性脑损伤海马神经元磷酸肌醇系统的变化及其机制的探讨  

Study of mechanism of alteration of phosphoinositide system in rat hippocampus during ischemic brain injury

作　　者：卢步峰[1] 黄森[1] 鲁友明 

机构地区：[1]镇江医学院生化研究室,海军神经生物学研究中心

出　　处：《中国病理生理杂志》1995年第5期488-491,共4页Chinese Journal of Pathophysiology

基　　金：江苏省自然科学基金

摘　　要：采用四动脉闭塞全脑缺血模型，观察大鼠缺血３０ｍｉｎ再灌注２１ｄ不同时间中，外源性谷氨酸（Ｇｌｕ）对海马脑片磷脂酰肌醇（ＰＩ）代谢的影响和偶联该系统的Ｇ蛋白功能变化。结果显示，Ｇｌｕ（５００μｍｏｌ／Ｌ）对正常和缺血再灌注海马脑片肌醇磷酸（ＩＰ）生成均具明显的促进作用（Ｐ＜０．０１，ｎ＝９），其中以缺血再灌注后ＩＰ的升高为显著，并且这种Ｇｌｕ刺激的ＩＰ堆积效应随缺血再灌注时间的延长在２１ｄ中持续存在。与此同时，还观察到缺血再灌注２４ｈ至７ｄ中，海马神经元Ｇｌｕ受体密度（Ｂｍａｘ）显著下降（Ｐ＜０．０１，ｎ＝８），亲和力（Ｋｄ）无显著变化。提示脑缺血再灌注后Ｇｌｕ刺激的ＰＩ代谢增强是由于Ｇｌｕ受体与磷脂酶Ｃ（ＰＬＣ）间产生高反应所致。应用四氟化铝（ＡｌＦ＿４￣－）可得到与上述Ｇｌｕ刺激ＩＰ生成相同的结果，而氨甲酰胆碱（Ｃａｈ）和去甲肾上腺素（ＮＥ）对ＩＰ水平的作用不受脑缺血和再灌注的影响。表明缺血状态下的这种Ｇｌｕ与ＰＬＣ间的高反应可能是特异的，并通过偶联该系统的Ｇ蛋白功能变化介导。Stimulation of phosphatidylinositol (PI)hydrolysis by glutamate(Glu)wasmeasured in hippocampal slices from rats receiving recovery periods of 21 day following30 min ischemic insult induced through a four- vessel occlusion model.The resultsshowed that PI hydrolysis elicited by Glu ( 500 μ)was significantly enhanced in theslices prepared from normal and ischemic rats(P<01,n=9). The effect was greater inslices from different periods(up to 21 day)after reperfusion than in slices from non- ischemic control.The hyperresponsiveness to Glu was always accompanied by an increasein AIF_4￣- -stimulated formation of￣3H-inositol phosphates.In addition,the availability ofan increased number or higher affinity of Glu receptors and the stimulation of PI hydro-lysis by carbachol or norepinephrine in the injured slices were not observed.These resu- lts suggested that the enhanced PI turnover responsiveness to Glu is the result,at least inpart,of functional changes at the G- protein level and may contribute to the pathophy-siology of ischemic brain injury or to the regenerative phenomena that accompany theischemic damage.

关 键 词：蛋白质 磷脂酰肌醇类 脑缺血 海马 神经元 

分 类 号：R743.310.2[医药卫生—神经病学与精神病学]