冷冻伤性脑水肿的发生机制及尼莫地平治疗作用的实验研究

Experimental Study of Mechanism of Brain Edema and Effects of Nimodipine on Brain Edema Following Freezing Injury

目的研究大鼠冷冻伤性脑水肿不同时间脑组织伊文思兰（ＥＢ）、突触体内［Ｃａ２＋］ｉ及Ｃａ２＋－ＡＴＰ酶活性变化与脑含水量变化之间的规律，以探讨冷冻伤性脑水肿的发生机制和类型。方法干湿法测定脑组织水分含量，甲酰胺法测定ＥＢ含量，Ｆｕｒａ－２／ＡＭ荧光标记法测定突触体内［Ｃａ２＋］ｉ，微量定磷法测定线粒体Ｃａ２＋－ＡＴＰ酶活性。采用尼莫地平进行治疗，研究其对ＥＢ含量、［Ｃａ２＋］ｉ、Ｃａ２＋－ＡＴＰ酶活性和脑水肿的影响。结果冷冻伤后３０分钟即已发生Ｃａ２＋超载，伴随Ｃａ２＋－ＡＴＰ酶活性下降及脑组织水分含量及ＥＢ含量增加。尼莫地平治疗后ＥＢ含量和［Ｃａ２＋］ｉ明显下降，而Ｃａ２＋－ＡＴＰ酶活性明显恢复，脑水肿明显减轻。结论ＢＢＢ的通透性增加和细胞内钙通道开放，钙离子浓度超载在脑水肿的发生与发展过程中起了重要作用。冷冻伤性脑水肿在早期既有细胞毒性脑水肿，又有血管源性脑水肿，即混合性脑水肿。

Aim To elucidate the mechanism and types of brain edema induced by freezing injury (FI). Methods [Ca^(2+) ]i was determined in calcium fluorescent in Fura 2/AM loaded neuronal synaptosomes by using mono wavelength spectrofluorophtometer. The Ca^(2+) ATPase activity was determined by biochemical method. Nimodipine was employed to show its effects on EB and WC of brain tissues, and on the [Ca 2+ ]i in the synaptosomes and alteration of Ca 2+ ATPase activity in the mitochondrial. Results Neurons had calcium overload at 30 minutes after FI. The level of WC and EB of brain tissues, and [Ca 2+ ]i significantly increased in the freezing cerebral hemisphere in the FI group as compared with that of the sham operation group at 30 minutes ( P <0.05). In the contrast, the activity of mitochondrial Ca 2+ ATPase decreased remarkably after FI ( P <0.05). There was close positive relationship between [Ca 2+ ]i and WC. But there was negative correlation between [Ca 2+ ]i and Ca 2+ ATPase. Conclusion It is suggested that the changes of the permeability of blood brain barries (BBB), [Ca 2+ ]i and Ca 2+ ATPase may participate in the pathogenesis of brain edema. Nimodipine through inhibiting the excess of Ca 2+ influx, stimulating the activity of Ca 2+ ATPase, and decreasing significantly [Ca 2+ ]i and the permeability of BBB and possess the protective effect on brain edema induced by FI.