二次脑损伤后大鼠脑皮层第Ⅲ组代谢型谷氨酸受体改变及意义

Changes and effects of group Ⅲ metabotropic glutamate receptors in the cerebral cortex of rats with diffuse brain injuries coupled with ischemic secondary brain insults

目的:为提高弥漫性脑损伤(DBI)及其合并缺血性二次脑损伤(SBI)的临床救治水平,研究DBI及其合并SBI后大鼠脑皮层第Ⅲ组代谢型谷氨酸受体(mGluRs)各亚型变化及意义。方法:SD大鼠175只,随机分为正常对照、假手术、单纯脑缺血、单纯DBI及DBI合并SBI组。在MarmarouDBI模型基础上,制成缺血性SBI模型,伤后1,6,12,24,72和168h进行皮层mGluR4,6～8mRNA原位杂交。结果:脑损伤后mGluR6表达无明显变化(P>0.05);与假手术组相比,单纯DBI及合并缺血性SBI组mGluR4、mGluR7和mGluR8mRNA转录在损伤1h后即有明显增加(P<0.05);单纯DBI组伤后6h达到高峰,7d后恢复正常;DBI合并SBI组伤后6h还在增加,12h达到高峰,单纯DBI组和合并缺血性SBI组之间差异有显著性意义(P<0.05)。结论:mGluR4、mGluR7和mGluR8参与脑损伤及缺血性SBI脑损害过程,可利用第Ⅲ组mGluRs特异性激动剂治疗DBI及其合并SBI。

AIM:To improve the clinical management of diffuse brain injuries(DBI) coupled with ischemic secondary brain insults(SBI), the changes and effects of groupⅢmetabotropic glutamate receptors(mGluR)after DBI with SBI in rats were studied.METHODS:Male SD rats were randomized into five groups: Normal control, Sham operated, cerebral ischemia alone, DBI alone and DBI coupled with SBI group.The SBI model was made on the basis of Mararou's model.The mRNAs of the mGluRs were detected at 1, 6,12,24,72 and 168 h after injuries by in situ hybridization.RESULTS:There were no significant mGluR6 mRNA changes in the rats' cerebral cortex after injury(P >0.05). The animals exposed to DBI with/without SBI showed a significant expression of mRNA of mGluR4, 7, 8 compared with the sham operated animals 1 h after injuries(P< 0.05). The expression reached the highest level in the DBI alone group at 6 h. But it still increased in the DBI with ischemic SBI group 6 h after injuries, and reached the peak at 12 h. In the same time, there was a significant increase of mGluRs in the DBI with ischemic SBI group than that in the DBI alone group(P< 0.05).CONCLUSION:It is indicated that the expression of mGluR4, 7,8 increased in DBI alone, and the changes come to be more significant when coupled with SBI, which may provide new therapies for severe brain injury.