兴奋性氨基酸和特异性受体对大鼠百日咳杆菌脑损伤的作用

目的 :探讨兴奋性氨基酸、N 甲基 D 天冬氨酸受体 (NMDAR)在大鼠百日咳杆菌脑损伤中的变化及作用机制。方法 :用高效液相色谱法、[3 H]MK 80 1放射配体结合分析法及Fura 2 /Am分别检测大鼠百日咳杆菌脑损伤时大脑皮质内谷氨酸 (Glu)和谷氨酰胺 (Gln)含量、NMDAR钙通道的结合位点 (最大结合位点Bmax)及活性 (平衡解离常数Kd)、大脑皮质突触细胞内游离钙浓度 ([Ca2 + ]i)的变化。结果 :与盐水组比较 ,注菌组Gln显著增高 (P <0 .0 5 ) ,Kd值减小 (P <0 .0 5 )、Bmax值差异无显著性 (P >0 .0 5 ) ,[Ca2 + ]i 较盐水组增高 (P <0 .0 1) ,并随注菌时间延长而显著增高 (2 4hvs 4h ,P <0 .0 1) ;MK 80 1预处理组 [Ca2 + ]i、脑含水量、伊文思蓝含量、Glu和Gln含量均较注菌组减少 (F值分别为 5 4 .2 4 36、15 .6 2 8、14 .4 2 5、10 .2 4 5 8、14 .0 2 34,P <0 .0 1) ,2 4h组 [Ca2 + ]i 减少最为显著 (P <0 .0 1)。结论 :EAAs介导的NMDAR激活及相应的钙内流增加在大鼠百日咳杆菌脑损伤中 ,尤其在百日咳杆菌致大鼠迟发性脑损伤的发病机制中可能起着重要作用。

Effects of excitatory amino acids and its specific receptor on bordetella pertussis brain injury of rats

Objective:To explore changes and mechanism of EAAs and its specific N-methyl-D-aspartate receptor(NMDAR) on bordetella pertussis brain injury in rats.Methods:Brain injury models were induced by injection of Bordetella pertussis suspension into left carotid artery in rats. The contents of glutamate(Glu) and glutamine(Gln),and binding sites labeled MK-801 of NMDAR and the alterations of the free calcium concentration ( i) in synaptosomes of cerebral cortexes in rats were measured by HPLC,and radioligand receptor binding and fluorospectrophotometer respectively.Results:Kd were significantly decreased(P<0.05),Gln and i were significantly increased(P<0.05,P<0.01) and i characterized in time-effect relationship(24 h vs 4 h,P<0.01),and Bmax of NMDAR was no differences in group treated by bordetella pertussis(BP) compared with contrast groups treated by normal saline(NS) or operative control(OC)(P>0.05),and that i water content,Evans blue content,contents of Glu and Gln were significantly decreased in group BP by pretreatment with MK-801 as compared with group BP(F values=54.2436,15.628,14.425,10.2458,14.0234,P<0.01 respectively).Conclusion:These findings suggest that activated NMDAR and its calcium influx overload induced by EAAs release maybe played an important role in brain injury of rats induced by bordetella pertussis,especially in delayed brain injury of rats.