丙泊酚与氯胺酮对老年大鼠远期记忆和大脑两种受体表达的比较∗

摘要

Objective To compare the effects of propofol and ketamine on long-term memory and the expression of brain N-methylgroup-D-aspartate receptor 2B(NMDAR2B) and Gamma-aminobutyric acid receptor 1(GABAR1) in aged rats, and preliminary investigate the relation between the long-term memory and expression of neurotransmitter receptors in different cerebral areas. Methods The aged male rats were randomly divided into control group,propofol group and ketamine group. Morris water maze training was performed in all the rats of three groups for 5 days. On the 6th day, intraperitoneal injection of 50 mg•mL-1 propofol was administrated in propofol group,80 mg•mL-1 ketamine was intraperitoneally injected in ketamine group,and blank control group was given the same dose of saline.Seven days after the administration,space exploration experiment and navigation experiment test were performed to test the impact on the learning and memory ability of rats. After that, the expression levels of GABAR1 and NMDAR2B in temporal lobe and hippocampal CA1 region of the rat brain were detected by immunofluorescence and FISH technique. Results The results of Morris water maze showed there was no significant difference between propofol group (9.49±1.24) s and blank control group (8.82±2.22) s.There was statistically significant difference between ketamine group (12.04±2.67) s and blank control group (P<0.05),with longer latency time and less number of times of passing through target as compared with blank control group.By using immunohistochemistry and FISH technique,the expression of GABAR1 in temporal lobe and hippocampal CA1 region of the rat brain was not significantly different between propofol group and blank control group,but it was significantly up-regulated in ketamine group as compared with blank control group ( P<0.05) . The expression of NMDAR2B in temporal lobe and hippocampal CA1 region of the rat brain was not significantly different between propofol group and blank control group,but it was significantly down-regulated in ketamine group as compared with blank control group (P<0.05). Conclusion Propofol anesthesia alone had no effect on long-term learning and memory,but ketamine anesthesia can result in long-term learning and memory impairment. The mechanism may be related with down-regulation of the expression of NMDAR2B receptor and up-regulation of GABAR1 not only in CA1 region hippocampus,but also in temporal lobe.%目的：通过比较丙泊酚和氯胺酮腹腔注射对老年大鼠远期记忆的影响及脑颞叶和海马CA1区N-甲基-D-天冬氨酸受体2B( NMDAR2B)和γ-氨基丁酸受体1( GABAR1)的表达，初步探讨远期记忆与不同脑区神经递质受体的关系。方法雄性老年大鼠随机分为空白对照组、丙泊酚组、氯胺酮组。3组大鼠于实验前进行为期5 d的Morris水迷宫训练，于第6天给药，丙泊酚组腹腔注射50 mg•mL-1丙泊酚，氯胺酮组腹腔注射80 mg•mL-1氯胺酮，空白对照组给予相同剂量的0.9％氯化钠溶液。给药后第7天进行空间探索实验及定位航行实验，测试对大鼠学习记忆能力的影响，测试结束后免疫荧光及FISH技术检测大鼠脑颞叶及海马CA1区GABAR1及NMDAR2B的表达。结果 Morris水迷宫结果：丙泊酚组(9.49±1.24) s与空白对照组(8.82±2.22) s比较，差异无统计学意义。氯胺酮组(12.04±2.67) s与空白对照组比较，差异有统计学意义( P<0.05)且较空白对照组潜伏期时间延长，穿越目标次数明显减少。免疫组化及FISH技术：大鼠脑颞叶及海马CA1区GABAR1表达：丙泊酚组与空白对照组比较，脑颞叶及海马CA1区均差异无统计学意义，而氯胺酮组与空白对照组比较，大鼠脑颞叶与海马 CA1区表达均明显上调( P<0.05)。大鼠脑颞叶及海马 CA1区NMDAR2B的表达：丙泊酚组与空白对照组比较，脑颞叶及海马CA1区均差异无统计学意义，而氯胺酮组与空白对照组比较，大鼠脑颞叶及海马CA1区表达均明显下降( P<0.05)。结论丙泊酚单独麻醉对长期的学习记忆无影响，而氯胺酮可导致麻醉长期学习记忆损伤，其机制可能不仅与海马CA1区NMDAR2B受体表达的下调和GABAR1表达的上调有关，其与颞叶等非海马区的受体表达也可能有关。