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运动训练对局灶性脑缺血大鼠学习记忆能力及弥散张量成像的影响①

缪培,张通,米海霞,张玉阁   

  1. 1. 首都医科大学康复医学院,北京市100068;2. 中国康复研究中心北京博爱医院,北京市100068。
  • 出版日期:2016-08-25 发布日期:2016-09-22

Effects of Exercise Training on Learning and Memory Ability and Diffusion Tensor Imaging in Rats after Focal Cerebral Ischemia

MIAO Pei, ZHANG Tong, MI Hai-xia , ZHANG Yu-ge   

  1. 1. Capital Medical University School of Rehabilitation Medicine, Beijing 100068, China; 2. Beijing Bo'ai Hospital, China Rehabilitation Research Center, Beijing 100068, China
  • Published:2016-08-25 Online:2016-09-22

摘要: 目的探讨运动训练对局灶性脑缺血大鼠学习记忆能力的影响,并运用弥散张量成像(DTI)参数分析运动训练后大鼠脑组织结构的变化。方法24 只SPF 级雄性Sprague-Dawley 大鼠随机分为假手术组(n=8)、自然恢复组(n=8)和运动训练组(n=8)。后两组根据Longa 改良线拴法制备大鼠左侧大脑中动脉闭塞(MCAO)模型。运动训练组于术后24 h 进行跑轮训练,共14 d。所有大鼠术后第15 天进行Morris 水迷宫测试。记录定位航行实验中三组大鼠到达平台的潜伏期,空间探索实验中三组大鼠第1 次到达平台所在位置的潜伏期、边界时间百分比、边界距离百分比、平均速度及游泳路径。各组选取Longa评分相近的4 只大鼠进行磁共振DTI扫描,测量脑缺血皮质及海马区域及对侧相应区域的部分各向异性(FA)、轴向扩散系数(λ‖)和径向扩散系数(λ⊥)。结果定位航行实验中,三组大鼠的潜伏期均随训练天数的增加呈下降趋势(P<0.05)。自然恢复组大鼠各时间点潜伏期均大于假手术组(P<0.05);运动训练组大鼠前3 d 潜伏期大于假手术组(P<0.05),第4、5 天潜伏期与假手术组无显著性差异(P>0.05),且小于自然恢复组(P<0.05)。空间探索实验中,自然恢复组大鼠潜伏期、边界时间百分比及边界距离百分比均明显大于假手术组(Z>2.627, P<0.01),边界时间百分比及边界距离百分比大于运动训练组(Z>2.521, P<0.05)。三组大鼠平均速度无显著性差异(P>0.05)。运动训练组和假手术组的游泳路径更优。假手术组大鼠左侧皮质感兴趣区FA及相对FA(rFA)均高于运动训练组和自然恢复组(P<0.05),运动训练组大鼠左侧皮质感兴趣区FA及rFA稍高于自然恢复组,但无显著性差异(P>0.05)。三组大鼠右侧大脑皮质感兴趣区FA无显著性差异(F=0.532, P=0.607)。假手术组大鼠左侧皮质感兴趣区λ⊥和λ‖及相对λ‖(rλ‖)和相对λ⊥(rλ⊥)均低于自然恢复组(P<0.05)。运动训练组大鼠左侧皮质感兴趣区λ⊥和λ‖及rλ‖和rλ⊥与自然恢复组及假手术组相比均无显著性差异(P>0.05)。三组大鼠右侧大脑皮质感兴趣区λ⊥和λ‖均无显著性差异(F<1.030, P>0.05)。三组大鼠双侧海马感兴趣区FA、λ‖及λ⊥及相对值均无显著性差异(F<1.845, P>0.05)。皮质感兴趣区rFA、rλ‖、rλ⊥及左侧λ⊥与空间探索实验中潜伏期相关(P<0.05),其中rλ⊥与潜伏期相关性较高(r=0.761, P<0.01)。结论适当的运动训练可改善局灶性脑缺血大鼠学习记忆能力,并可促进其皮质缺血区神经纤维损伤修复和减轻血管源性水肿。DTI 参数中,皮质的rFA、rλ‖、rλ⊥及患侧皮质区λ⊥可能是大鼠局灶性脑缺血后认知功能恢复的有效预测指标,其中rλ⊥的预测价值更高。

关键词: 局灶性脑缺血, 运动训练, 学习记忆能力, 弥散张量成像

Abstract: Objective To explore the effect of exercise training on learning and memory ability in rats with focal cerebral ischemia, and to analyze the changes of brain tissue structure of rats after exercise training through diffusion tensor imaging (DTI). Methods Twenty-four SPF male Sprague-Dawley rats were randomly divided into sham operation group (n=8), natural recovery group (n=8) and exercise training group (n=8). The left middle cerebral artery occlusion (MCAO) model was established. The exercise training group received running wheel training 24 hours after modeling, for 14 days. All groups were tested by the Morris water maze 15 days after modeling. The latency in the navigation experiment, as well as the first latency, boundary swimming time ratio, the boundary swimming distance ratio, the average speed and the swimming path in the space exploration experiment were recorded. Four rats with similar Longa scores in each group received routine magnetic resonance imaging and DTI scanning, the fractional anisotropy (FA), axial diffusivity (λ‖), and radial diffusivity (λ⊥) of isch-emic cortex and hippocampal lesion and contralateral side were measured. Results In the navigation experiment, the latency of three groups showed a downward trend along with training days (P<0.05). The latency was longer in all the time points in the natural recovery group than in the sham operation group (P<0.05), and was longer in the first three days in the exercise training group than in the sham operation group (P<0.05), however, there was no significant difference between them in the last two days (P>0.05), while it was shorter in the exercise training group than in the natural recovery group in the same time (P<0.05). In the space exploration experiment, the latency, the boundary swimming time ratio and the boundary swimming distance ratio were more in the natural recovery group than in the sham operation group (Z> 2.627, P<0.01), and the latter two indexes were also higher in the natural recovery group than in the exercise training group (Z>2.521, P< 0.05). No significant difference was found in the average speed among three groups (P>0.05). The swimming paths in the exercise training group and the sham operation group were better than that of the natural recovery group. The FA and rFA in the left cortical area were higher in the sham operation group than in the exercise training group and the natural recovery group (P<0.05), however, no significant difference was found between the exercise training group and the natural recovery group (P>0.05). There was no significant difference in the FA in the right cortical area among three groups (F=0.532, P=0.607). The λ⊥, λ‖, rλ‖ and rλ⊥ in the left cortical area were lower in the sham operation group than in the natural recovery group (P<0.05), and no significant difference was found from the exercise training group to the natural recovery group, nor to the sham operation group (P>0.05). There was no significant difference in the λ⊥ and λ‖ in the right cortical area among three groups (F<1.030, P>0.05). There was no significant difference in the FA, λ⊥, λ‖ and rFA, rλ⊥ and rλ‖ in the bilateral hippocampal interest area among three groups (F<1.845, P>0.05). The rFA, rλ‖, rλ⊥ and left λ⊥ were correlated with the latency in the space exploration experiment in the Morris water maze test (P<0.05), in which the correlation coefficient of rλ⊥ was the highest (r=0.761, P<0.01). Conclusion Proper exercise training can improve the learning and memory ability of rats with focal cerebral ischemia, and can promote the repair of nerve fiber damage and reduce the vascular edema. In addition, the rFA, rλ‖, rλ⊥ and λ⊥ of ischemic cortex may be predictors of cognitive function recovery in rats after focal cerebral ischemia, especially rλ⊥.

Key words: focal cerebral ischemia, exercise training, learning and memory ability, diffusion tensor imaging