Centrophenoxine improves chronic cerebral ischemia induced cognitive deficit and neuronal degeneration in rats.
Centrophenoxine improves chronic cerebral ischemia induced cognitive deficit and neuronal degeneration in rats.
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发表时间：
2004-12
影响因子：
8.2
通讯作者：
Y. Liao;Rui Wang;Xi-can Tang
中科院分区：
文献类型：
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作者：
Y. Liao;Rui Wang;Xi-can Tang
目的研究中心苯酚辛（CPH，甲氯芬酯）对大鼠慢性脑灌注不足所致的脑损伤的影响。方法通过永久结扎双侧颈总动脉来造成大鼠慢性低灌注。莫里斯水迷宫用于测量空间记忆表现。使用分光光度技术测定 SOD、GPx 活性、MDA 含量、TXB2 和 6-keto-PGF1α 水平。通过HE染色检查形态变化。通过免疫组织化学分析检测Bax和p53蛋白的表达。结果 大鼠慢性灌注不足会导致空间记忆受损，表现为逃避潜伏期较长和在目标象限中停留的时间较短。这些行为功能障碍伴随着SOD和GPx活性、MDA含量、促炎介质（TXB2、6-keto-PGF1α）水平的增加、Bax和P53蛋白的过度表达以及皮层和海马神经元的延迟退化。口服CPH（100 mg/kg，每天一次，连续37 d）可显着改善记忆障碍，使抗氧化酶活性、MDA含量和促炎介质水平的增加降低至正常水平，并减轻神经元损伤。结论 CPH 减轻缺血后记忆缺陷和神经元损伤的能力可能对脑血管型痴呆有益。
AIM To study the effects of centrophenoxine (CPH, meclofenoxate) on chronic cerebral hypoperfusion induced deficits in rats. METHODS Chronic hypoperfusion in rats was performed by permanent bilateral ligation of the common carotid arteries. Morris water maze was used to measure spatial memory performance. Spectrophotometrical techniques were used to assay SOD, GPx activities, MDA content, TXB2, and 6-keto-PGF1alpha levels. Morphological change was examined by HE staining. The expression of Bax and p53 protein were assayed by immunohistochemistry analysis. RESULTS Chronic hypoperfusion in rats resulted in spatial memory impairments shown by longer escape latency and shorter time spent in the target quadrant. These behavioral dysfunction were accompanied by increase in SOD and GPx activities, the content of MDA, the levels of pro-inflammatory mediators (TXB2, 6-keto-PGF1alpha), overexpression of Bax and P53 protein, and delayed degeneration of neurons in cortex and hippocampus. Oral administration of CPH (100 mg/kg, once per day for 37 d) markedly improved the memory impairment, reduced the increase in antioxidant enzyme activities, MDA content and the levels of pro-inflammatory mediators to their normal levels, and attenuated neuronal damage. CONCLUSION The abilities of CPH to attenuate memory deficits and neuronal damage after ischemia may be beneficial in cerebrovascular type dementia.