尼莫地平和MK-801对感染性脑水肿的保护作用

Protective effects of nimodipine and MK-801 on brain edema induced by injection of Pertussis Bacilli.

目的观察尼莫地平和MK-801对感染性脑水肿的影响。方法采用百日咳菌液诱导的感染性脑水肿模型,干湿法测定脑组织水份含量,甲酰胺法测定EB含量,Fura-2/AM荧光标记法测定突触体内[Ca^(2+)]_i,微量定磷法测定线粒体Ca^(2+)-ATP酶活性。结果菌液组注菌侧神经元细胞内钙离子超载,伴随Ca^(2+)-ATP酶活性下降。脑含水量随EB含量的增加和[Ca^(2+)]_i的升高及Ca^(2+)-ATP酶活性下降而增加。应用MK-801预处理或尼莫地平治疗后,脑组织含水量和EB含量及突触体内[Ca^(2+)]_i明显下降,而Ca^(2+)-ATP酶活性明显升高。结论尼莫地平通过降低BBB的通透性和[Ca^(2+)]_i及恢复Ca^(2+)-ATP酶活性;MK-801通过阻断NMDA受体介导的迟发性钙离子内流,对感染性脑水肿均有保护作用。

Objective To investigate the changes in the water content and Evan blue (EB) of brain tissues, and concentration of cytosolic free calcium ([Ca^(2+)]_i, in the synaptosomes and activity of mitochondrial Ca^(2+)- ATPase at different time points on the model of brain edema induced by injection of Pertussin Bacilli (PB). Methods Pretreatment of MK-801, nimodipine was administered to show its effects on brain edema induced by injection of PB. Water content and the concentration of EB were quantitatively measured. [Ca^(2+)]_i was determined in calcium fluorescent indicator Fura-2/AM loaded neuronal synaptosomes by using mono-wave length spectrofluorophotometer, Ca^(2+)-ATPase activity by biochemical method. Results The water content and EB level of brain tissues and [Ca^(2+)]_i were significantly increased in the injected PB cerebral hemisphere in the PB group as compared with that of NS group (P<0.05). However, after the pretreatment of MK-801 or nimodipine treatment the activity of mitochondrial Ca^(2+)-ATPase was remarkably increased, at the same time the levels of [Ca^(2+)]_i in the synaptosomes and water content and EB of brain tissues were obviously decreased in the injective cerebral hemispere as compared with that of PB group. Conclusion Both nimodipine and MK-801, the former decreasing the permeability of blood-brain barrier and stimulating the activity of Ca^(2+)-ATPase and the latter blocking the excess of delayed Ca^(2+) influx mediated by NMDA receptors, had protective effects on the brain edema induced by injection of PB.