不同剂量氯胺酮对老年大鼠认知功能的影响  

Effects of different doses of ketamtne on cognitive function in aged rats

作　　者：陈晨[1] 桂波[1] 钱燕宁[1] 

机构地区：[1]南京医科大学第一附属医院麻醉科,210029

出　　处：《中华麻醉学杂志》2008年第7期590-593,共4页Chinese Journal of Anesthesiology

摘　　要：目的探讨腹腔注射不同剂量氯胺酮对老年大鼠认知功能的影响。方法老年SD大鼠40只，15月龄，体重470～570g，雌雄各半，随机分为4组（n=10），对照组（C组）腹腔注射生理盐水2ml，K1组、K2组和K3组分别腹腔注射氯胺酮10、20和100mg／kg（溶于2ml生理盐水），连续3d。于停药后1d（T1）、2d（T2）、3d（T3）行水迷宫实验，记录潜伏期及游泳路程。末次水迷宫测试结束后1h处死大鼠，采用RT-PCR法测定海马N-甲基-D-天门冬氨酸（NMDA）受体亚基NR1 mRNA和NR2 BmRNA的表达，免疫组织化学法测定海马NR1和NR2B蛋白的表达。结果与T1时比较，C组和K2组T2.3时、K1.3组T3时潜伏期缩短，C组T2．3时、K1.2组T3时游泳路程缩短（P〈0．05）；与C组比较，K3组T2.3时潜伏期和游泳路程延长，K1组NR2B蛋白表达上调，K3组NR2B mRNA及蛋白表达下调（P〈0．05）；各组NR1 mRNA及蛋白表达差异无统计学意义（P〉0．05）。结论亚麻醉剂量氯胺酮对老年大鼠认知功能无明显影响，而麻醉剂量氯胺酮可致老年大鼠认知功能减退，其机制可能与含NR2B亚基的NMDA受体表达下调有关。Objective To investigate the effects of different doses of ketamine on spatial cognitive function and the expression of mRNA and protein of N-methyl-D-aspartate （NMDA） receptor subunits NR1 and NR2B in the hippocampus of aged rots. Methods Forty SD rats of both sexes aged 15 months weighing 470-570 g were randomly divided into 4 groups （ n = 10 each） ： one control group （C） and three ketamine groups （ K1, K2, K3 ）. The animals in group K1, K2 and K3 received intraperitoneal （IP） ketamine 10, 20 and 100 mg/kg respectively once a day for 3 days, whereas the animals in control group received IP normal saline instead of ketamine. One day after the last drug administration, the animals underwent Morris water maze test 4 times a day for 3 consecutive days. The animals were killed within 1 h after the last test for determination of the expression of NR1 mRNA and NR2B mRNA （using RT-PCR） and protein （using immuno-histochemistry） in the hippocampus. Results The latency period and swimming distance of water maze test were significantly longer on the 2nd and 3rd days in group K3 than in control group. The NR2B mRNA and protein expression was significantly lower in group K3 than in control group. Conclusion Anesthetic dose of ketamine decreases spatial cognitive function and the expression of NR2B mRNA and protein in aged rats whereas subanesthetic doses of ketamine do not.

关 键 词：氯胺酮 认知障碍 受体 N-甲基-D-天冬氨酸 老年人 

分 类 号：R96[医药卫生—药理学]