弥漫性脑损伤后代谢型谷氨酸受体亚型4及其激动剂L-AP 4的作用

目的　研究弥漫性脑损伤 (DBI)后大鼠脑皮质代谢型谷氨酸受体亚型 4 (mGluR 4 )及其激动剂L 2 氨基 4 膦酰基丁酸(L AP 4 )的变化及意义。方法　 16 1只SD大鼠随机分为两组。A组包括正常对照组、假手术组及DBI组。用Marmarou弥漫性脑损伤模型 ,制成DBI模型 ,于伤后不同时间进行mGluR 4mRNA原位杂交。B组包括单纯、DBI后生理盐水治疗及DBI后L AP 4治疗组。所有DBI动物伤前进行行为学训练。伤后 1h、12h脑室内分别给予L AP 4 (10 0mM ,10 μl)或生理盐水。大鼠在伤后 1、3、7、14d分批处死前进行运动和行为学检查 ,处死后检测神经元损伤数。结果　与正常对照组相比 ,假手术组阳性神经元数无改变 (P >0 .0 5 ) ;与假手术组相比 ,单纯DBI组mGluR 4mRNA表达于脑损伤后 1h即有明显增加(P <0 .0 1) ,在 6h达到高峰。与DBI后生理盐水治疗组比较 ,DBI后L AP 4治疗组神经元损伤数减少 ,神经功能检查指数增高。结论　mGluR 4参与了DBI的病理生理过程 ,具有神经保护作用。

The roles of mGluR 4 and its agonist L-AP 4 following diffuse brain injury

Objective The focus of this study is to examine the roles of mGluR 4 after diffuse brain injury(DBI) and its specific agonist L-AP 4.Methods 161 male SD rats were randomized into two groups. Group A included normal control, sham-operated control and DBI group. DBI was produced by Marmarou's diffuse brain injury model. The mRNA expression of mGluR 4 was detected by hybridization in situ. Group B included DBI alone, DBI treated with normal saline and DBI treated with L-AP 4. All DBI rats were first trained in a series of performance tests before they were subjected to DBI. At 1 and 12 h, animals were injected intracerebroventricularly with L-AP 4(100 mM, 10 μl) or normal saline respectively. The rats were tested for motor and cognitive performance respectively at 1, 3, 7, 14 d post injury and then were killed for detecting the damaged neurons.Results There was no significant difference between normal control group and sham-operated group in the expression of mGluR 4(P>0.05). The animals exposed to DBI showed a significantly increased expression of mRNA of mGluR 4 compared with the sham-operated animals 1 h after injury(P<0.05). At 6 h, the evolution of neuronal expression of mGluR 4 in the trauma alone group was relatively static. Compared with saline-treated control animals, the rats treated with L-AP 4 showed decreased number of damaged neurons and a better motor and cognitive performance.Conclusion It is indicated that the increased expression of mGluR 4 is an important process in the pathophysiological changes of DBI and its specific agonist L-AP 4 can provide a remarkable neuroprotection.