弥漫性脑创伤与二次脑损伤发生机制研究

A STUDY ON THE MECHANISM OF DIFFUSE BRAIN INJURY WITH SECONDARY BRAIN INSULT

为研究弥漫性脑创伤 (DBI)与二次脑损伤 (SBI)后鼠脑代谢型谷氨酸受体 1a(mGluR1a)、cAMP、cGMP含量变化及I类mGluRs拮抗剂MCPG的治疗作用 ,将大鼠随机分为假手术对照、单纯DBI、脑损伤合并SBI及MCPG作用组。脑损伤后 ,以低血压作为SBI指标 ,于伤后不同时间进行免疫组化和放射免疫研究。结果发现 ,与对照组比较 ,单纯DBI组脑皮层mGluR1a阳性神经元表达在伤后 1h增加 ,2 4h达高峰 (P <0 .0 1) ,伤后2 4hcAMP水平下降 ,cGMP升高 ,cAMP/cGMP比值下降 ;合并SBI组 ,mGluR1a阳性神经元表达在伤后 0 5h即明显增加 ,6h达高峰 (P <0 0 1) ,cAMP改变也更加明显 ;MCPG可减少SBI后损伤神经元的数目。提示mGluR1a参与了细胞兴奋性毒性和代谢应急 ,是加重脑损害的关键因素。

To study the changes in metabotropic glutamate receptor subtype mGluR1a and cAMP、cGMP, as well as the effect of groupⅠantagonist MCPG in diffuse brain injury (DBI) with secondary insults(SBI). Based on Marmarou’s rodent model of diffuse brain injury, hypotension was chosen as the SBI. SD rats were randomized into sham, DBI alone, head injury with SBI and MCPG treatment groups. Expression of mGluRla in cerebral cortex was assayed with immunohistochemistry and immunoradioassay at different time intervals after brain injury .It was showed that compared with that of sham group, mGluR1a expression positive neurons increased 1h after injury, and it peaked at 24h after injury( P <0 01)in DBI alone group.However, in head injury with SBI group there was a significant increase of the expression of mGluR1a positive neurons at 0 5h after injury, peaking at 6 hours after injury( P <0 01).The levels of cAMP and the ratio of cAMP to cGMP ( P <0 01)declined at 24 hours after DBI, while that of cGMP( P <0 01) increased. All these changes aggravated in SBI group. Administration of MCPG reduced total cortical necrotic neuron counts on the 7d after DBI.It is concluded that in the development of DBI and SBI mGluR1a plays an important role in the aggravation of brain damage.