盐酸美金刚对血管性痴呆大鼠CREB和细胞色素c表达的影响

Effects of memantine hydrochloride on the expressions of cAMP responsive element binding protein and cytochrome c in vascular dementia in rats

目的探讨盐酸美金刚对血管性痴呆（vascular dementia，VaD）大鼠学习记忆功能的影响和可能机制。方法采用双侧颈总动脉永久结扎法建立大鼠VaD模型。36只SD大鼠分为假手术组、VaD组和美金刚组（灌胃给予盐酸美金刚，1次／d，连续8周），每组12只。用Y型迷宫试验观察其行为学改变，用免疫组化技术检测大鼠海马CA1区和皮质神经元环磷酸腺苷反应元件结合蛋白（cAMP responsive element binding protein,CREB）和细胞色素c（cytochrome c，CytC）表达变化，TUNEL染色检测神经元凋亡情况。结果美金刚组学习和记忆成绩分别为（50．17±5．56）次和（7．08±0．90）次，显著优于VaD组的（66．36±5．41）次和（4．64±1．03）次（P均〈0．01）；海马CA1区和皮质CREB平均吸光度分别为147．5l±7．11和155．37±4．52，显著高于VaD组的135．11±8．52和142．39±5．24（P均〈0．01）；海马CA1区和皮质CytC平均吸光度分别为116．53±4．91和113．51±6．05，照著低于VaD组的136．65±7．43和138．09±4．88（P均〈0．01）；美金刚组细胞凋亡程度也较VaD组明显改善。结论盐酸美金刚可能通过上调CREB表达、抑制CytC释放和神经元凋亡来改善VaD大鼠的学习记忆功能。

Objeetive To investigate the effects of memantine hydrochloride on the learning and memory function in vascular dementia （VaD） in rats and its possible mechanism. Methods A rat VaD model was induced by using permanent bilateral common carotid artery ligation. A total of 36 SD rats were randomly divided into sham-operation group, VaD group, and memantine group （memantine hydrochloride was given by intragastric administration, once a day, for eight weeks） （n = 12 in each group）. Y maze test was used to observe their behavioral changes, lmmunohistochemistry technique was used to detect the changes of the expressions of cAMP respousive element binding protein （CREB） and cytochrome c （CytC） in hippocampal CAI region and cortex; and TUNEL method was used to detect neuronal apoptosis. Results The learning and memory abilities in memantine group were 50. 17 ± 5.56 and 7.08 ± 0.90 respectively, and they were significantly better than 66.36 ± 5.41 and 4.64 ± 1.03 in the VaD group （all P 〈0.01）; the mean absorbencies of CREB in hippocampal CA1 region and cortex were 147.51 ± 7. 11 and 155.37 ± 4.52, respectively, and they were significantly higher than 135.11 ± 8.52 and 142.39 ± 5.24 in the VaD group （all P 〈0.01）; and the mean absorbencies of CytC in hippocampal CA1 region and cortex were 116.53±4.91 and 113.51±6.05, and they were significantly lower than 136.65±7.43 and 138.09±4.88 in the VaD group （all P 〈 0.01 ）; the extent of apoptosis in the memantine group was also improved significantly compared to the VaD group. Conclusions Memantine hydrochloride may improve the learning and memory function in VaD rats by upregulating the expression of CREB and inhibiting the release of CytC and neuronal apoptosis.