亚低温对大鼠局灶性脑缺血后细胞凋亡及Caspase-3的影响

目的 探讨亚低温对脑缺血损伤的保护作用。方法 用原位末端标记（TUNEL）和原位杂交技术分别观察亚低温组、常温组脑缺血不同时间点神经细胞凋亡的变化及Caspase-3的表达。结果 （1）常温组脑缺血后凋亡神经细胞主要分布于缺血周围区，随着时间的延长凋亡细胞数逐渐增加，至12h达高峰，24h后开始下降，7d时仍高于假手术组；（2）亚低温组脑缺血后，凋亡神经细胞也主要位于缺血周围区，数量相对较少，其变化规律与常温组相似，同一时间点相比较，亚低温组均显著低于常温组；（3）常温组脑缺血2h后，神经细胞Caspase-3开始表达，并随着时间的延长而增强，24h达高峰，其后逐渐下降，至7d略高于假手术组；（4）亚低温组脑缺血后，神经细胞Caspase-3的表达也主要位于缺血周围区，其变化规律与常温组相似，同一时间点相比较，亚低温组均显著低于常温组。结论 脑缺血后，缺血周围区神经细胞的凋亡是一个动态的渐进过程，Caspase-3基因在介导脑缺血损伤神经元凋亡过程中起关键作用。亚低温对短暂性脑缺血后的神经元凋亡有明显的抑制作用，亚低温可能通过Caspase-3途径抵抗脑缺血损伤。

Effect of mild hpothermia on the apoptosis and expression of Caspase- 3 in rats with focal cerebral ischemia

Objective To explore the protective effects of mild hypothermia on focal cerebral ischemia in rats.Methods All of the rats were randomly divided into three groups: mild hypothermia group,normalthermia group and sham-oprative group.The neuronal apoptosis and expression of caspase-3 in each group were dynamically detected by TUNEL,and in situ hybridization respectively.Results(1)After ischemia in rats in normalthermia group,apoptosis was obviously found in the peripheral area of ischemia.The number of apoptotic cells increased with time,reached its height in 12 hours,and reduced after 24 hours.At the time of 7d after ischemia,the number of apoptotic cells was still larger than that of sham-operative group.(2) In mild hypothermia group,the apoptosis was also in the peripheral area of ischemia,but the number was less compared with that of normalthermia.The regularity of change for apoptosis was similar to that of normalthermia group.the apoptotic percentage was obviously less than normalthermia group.(3) The expression of caspase-3 in neuronal cells was found in normalthermia group at 2 hours after ischermia,increased with time,reached peak at 24 hours,and reduced after that point.At the time of 7d after ischemia,the expression was slightly higher than that of sham-operative group.(4) After ischemia in mild hypothermia group,the expression of caspase-3 was found in the peripheral area of ischmia,and the change was similar to that of normalthermia group.At the same time point,the expression was significantly lower than that of normalthermia group.(Conclusions)After ischemia,the cell apoptosis in the peripheral area of ischemia was a dynamic developing course.The caspase-3 gene plays an important role in mediating the apoptosis after ischemia injury.Mild hypothermia might restrain the cell apoptosis after cerebral ischemia injury significantly.