体温增高对新生大鼠缺氧缺血性脑损伤后学习记忆功能的影响

Effect of hyperthermia on ability of spatial learning and memory after neonatal hypoxia-ischemia brain damage

目的探讨体温增高对新生大鼠缺氧缺血性脑损伤(HIBD)后学习记忆功能的影响。方法新生7日龄SD大鼠62只,随机分为高温HIBD组、常温HIBD组、单纯高温组和常温对照组。高温HIBD组予以42℃缺氧缺血处理,常温HIBD组予以37℃缺氧缺血处理,缺氧时间60 min。单纯高温组置于42℃水浴箱中60 min而不进行缺氧处理,常温对照组不进行任何处理。4周后利用Morris水迷宫实验评估大鼠空间学习记忆能力,后断头取脑,进行鼠脑大体形态学评分,并使用透射电镜观察各组鼠脑损伤部位神经元突触超微结构的改变。结果单纯高温组各项检测指标与常温对照组比较差异均无统计学意义(P>0.05),常温HIBD组及高温HIBD组与常温对照组比较,逃避潜伏期(s)延长[第1天:(75.1±5.7)、(75.7±2.2)比(71.3±6.0),第2天:(60.9±6.7)、(62.0±5.0)比(55.0±4.5),第3天:(58.2±6.0)、(65.2±11.5)比(47.6±8.9),第4天:(44.2±5.7)、(48.6±3.5)比(33.1±4.0)],穿台次数(次)减少[(3.1±1.2)、(2.1±1.0)比(3.8±1.2)],脑组织形态学评分(分)增加[(2.1±1.0)、(2.9±1.0)比(0.0±0.0)],透射电镜观察突触间隙增宽[(21.9±2.0)、(23.5±2.0)比(19.3±1.2)],P均<0.05,高温HIBD组比常温HIBD组改变更加明显,差异有统计学意义(P<0.05)。结论体温增高加重新生大鼠HIBD程度,严重影响空间学习记忆能力,而单纯体温增高不会造成新生大鼠远期学习记忆能力下降。

[ Abstract] Objective To investigate the effect of hyperthermia on the ability of spatial learning and memory in the rat model of neonatal hypoxic-ischemia brain damage. Methods Total of 62 7-day- old neonatal Sprague-Dawley rats, were divided into four groups randomly： hyperthermia hypoxia- ischemia brain damage group （ HHIBD group, n = 20 pups）, normothermic hypoxia-ischemia brain damage group （NHIBD group, n = 20 pups）, hyperthermia alone group （H group, n = 11 pups） and normothermic group（ N group, n = 11 pups）. Neonatal rats underwent a combination of left common carotid hypoxic artery ligation and exposure to 8% oxygen for 60 minutes （rt =40 rats）. During the 60-minute damage, temperature was elevated to 42 ℃ in 20 animals （ HHIBD group）, and was maintained at 37℃ in 20 animals （NHIBD group ）. The H group was placed in a water bath in which the temperature was kept at 42℃ for 60 minutes without hypoxic exposure. Four weeks later, all rats had spatial learning and memory evaluated by the Morris Water Maze. Then, the brains were removed and scored for macroscopic brain injury. The uhrastructure was observed with transmission electron microscope（TEM）. Results There were no differences between H group and N group （P 〉 0. 05 ）. Compared with N group, NHIBD group and HHIBD group showed significant brain injury, the escape latency was longer [D1：（75.1 ±5.7）, （75.7±2.2）, （71.3 ±6.0）, D2：（60.9_±6.7）, （62.0± 5.0）, （55.0±4.5）,D3：（58.2±6.0）, （65.2±I1.5）, （47.6 ±8.9）, D4：（44.2 ±5.7）, （48.6± 3.5） , （33. 1 ±4.0） ] , the number of through the platform was reduced [ （3.1 ± 1.2） , （2. 1 ± 1.0） , （ 3.8 ± 1.2） ]. The macroscopic brain injury score was increased [ （2. 1 ± 1.0）, （2. 9 ± 1.0）, （0. 0 ± 0. 0） ] ; TEM showed the synaptic cleft was widened [ （21.9 ± 2.0 ）, （ 23.5 ± 2. 0 ）, （ 19.3 ± 1.2） ], P 〈0. 05. HHIBD group was more seriously compromised than the NHIBD group （P 〈 0. 05 ）. Conclusions Hyperthermia worsens neonatal hypoxia-ischemia brain damage, impairs the ability of spatial learning and memory seriously, hyperthermia alone does not cause a decline in learning and memory abilities.