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目的探讨氯化钴(cobalt chloride,CoCl2)后处理对缺氧缺血性脑损伤新生大鼠空间学习记忆的作用。方法生后7日龄SD大鼠66只,分为假手术组(n=16)、缺氧缺血组(HI组,n=18)、CoCl2即刻干预组(C1组,n=14)、CoCl2术后1 d干预组(C2组,n=18)。Western blot检测术后1、2、7 d脑组织HIF-1α蛋白的表达。大鼠生后7周行水迷宫观察CoCl2对大鼠空间学习记忆的影响。结果 HI组和C1组HIF-1α蛋白在术后第1、2天增多,第7天则不能检测到HIF-1α蛋白。而C2组第7天仍能检测到HIF-1α蛋白表达。水迷宫实验显示C2组较HI组3～5 d时平均潜伏时间明显缩短,穿越原平台区域的时间增加,空间学习记忆能力部分恢复(P<0.05)。结论在新生鼠缺氧缺血性脑损伤时,CoCl2促进HIF-1α蛋白的持续表达,术后1 d干预可有效恢复大鼠的空间学习记忆能力。
Objective To investigate the effect of cobalt chloride (CoCl2) postconditioning on spatial learning and memory in neonatal rats with hypoxic-ischemic brain damage. Methods Sixty-six SD rats aged 7 days after birth were divided into sham operation group (n = 16), hypoxic-ischemic group (HI group, n = 18), CoCl2 immediate intervention group (n = 14) One day after CoCl2 treatment, the intervention group (C2 group, n = 18). Western blot was used to detect the expression of HIF-1α protein at 1, 2 and 7 days after operation. Effects of CoCl2 on spatial learning and memory of rats induced by water maze at 7 weeks after birth. Results HIF-1αprotein in HI group and C1 group increased on the 1st and 2nd day after operation, while HIF-1αprotein was not detected on the 7th day. On the 7th day in C2 group, HIF-1α protein expression was still detected. The water maze test showed that the average latency time of C2 group was significantly shorter than that of HI group at 3 ~ 5 d, and the time of crossing the original platform area was increased, and the learning and memory ability of space was partly recovered (P <0.05). Conclusions CoCl2 can promote the sustained expression of HIF-1α protein in neonatal rats with hypoxic-ischemic brain damage. One-day postoperative intervention can effectively restore spatial learning and memory in rats.