右美托咪定对术后老龄小鼠海马组织caspase-3、Bax表达的影响

Effects of dexmedetomidine on postoperative expressions of caspase-3 and Bax in hippocampus tissues of aged mice

目的 探讨右美托咪定（dexmedetomidine，Dex）对手术创伤后老年小鼠caspase-3、Bax表达水平及术后认知功能障碍（postoperativecognitivedecline，POCD）的影响。方法健康老龄昆明小鼠105只，13～15月龄，体重45～55g。采用随机数字表法分为4组：空白对照组（c组，15只）；麻醉药物组（A组，30只），实验动物接受异氟醚、氯胺酮药物达到相应手术麻醉深度，给药后第1天和第3天分别设为A1组、A3组；麻醉药物手术组（P组，30只），实验动物接受复合麻醉药物后实施剖腹探查脾切除手术，术后第1天和第3天分别设为P1组、P3组；Dex干预组（D组，30只），术前30min各取15只小鼠分别给予Dex15、25μg／kg腹腔内注射（D15组、D25组）。术后第1天、第3天行Y迷宫试验观察神经行为学改变（Dex干预组术后第3天进行）；Westernblot和免疫组化检测各组海马组织caspase-3、Bax表达。结果Y迷宫试验中，与C组（27＋8）比较，A组术后第1天[（50＋10）次]、P组术后第1天[（70±15）次]和第3天[（65±16）次训练次数增加，差异有统计学意义（P〈0．01，P〈0．05），D15，组、D25组术后第3天与C组比较，差异无统计学意义（P＞0．05）；与P组第3天[（65±16）次]比较，D25组[（29±6）次瑚I练次数差异有统计学意义（P〈0．05）与C组比较，A组、P组术后第1天、第3天caspase-3、Bax蛋白的表达量及阳性细胞数升高（P〈0．01／9〈0．05）；D。D。组第3天与C组caspase-3、Bax蛋白的表达量及阳性细胞数比较，差异无统计学意义（P〉0．05）。与P组第3天比较，D15、D25组caspase-3、Bax蛋白表达量及阳性细胞数降低（P〈0．01，P〈0．05o结论Dex预处理能降低caspase-3、Bax蛋白的表达量及阳性细胞数，减弱海马神经细胞损伤，从而改善小鼠POCD。

Objective To explore the effects of dexmedetomidine （Dex） on expressions of caspase-3 and Bax in hippocampus tissues of aged mice after surgery and postoperative cognitive dysfunction （POCD）. Methods A total of 105 aged Kunming mice were randomly divided into 4 groups： control group （C group, n=15） that received no anesthesia and surgery, anesthesia group （A group, n=30） that received 1.5% to 2% consecutive isoflurane inhalation for 60 min combined with intraperitoneal injection of 100 mg/kg ketamine on 1 d （A1 group） and 3 d （A3 group） after surgery, splenectomy group （P group, n=30） that undergoing splenectomy under the same anesthesia as in A group named P1 group and P3 group, intervention group （D group, n=30） that received intraperitoneal injection of Dex of 15μg/kg and 25 μg/kg （15 mice for each dose as D15, D25） for 30 min before anesthesia and surgery. Y.maze experiments were conducted on 1 d and 3 d after surgery to investigate the neuro-behavioral differences （Y-maze experiments were conducted on 3 d after surgery for D group）. The frequencies of training of each group were recorded. The protein expression and positive cells of Bax and caspase-3 in hippocampus tissues were detected by Western blot and Immunohistochemistry assay respectively. Results Compared to C group（27±8）, on day 1 after surgery in anesthesia group（50±10）, and on day 1 and 3 after surgery in P group[（70±15）, （65±16）], training times were increased in the training frequencies（P〈0.01, P〈0.05）. No significant difference was seen between D groups （D25, D15 group） and control group（P〉0.05）. Compared with P3 group（65±16）, the training frequency of D25 group （29±6） was significantly different （P〈0.05）. Compared with the C group, caspase-3 and Bax protein expression and positive cells in hippocampus tissues in anesthesia and splenectomized group were significantly increased on 1 d and 3 d after surgery （P〈0.01, P〈0.05）, especially in splenectomy group. The differences between the intervention groups （D15, Dz） and control group were not statistically significant on 3 d after surgery （P〉0.05）. Compared with the splenectomy group 3 d after surgery, Caspase-3 and Bax protein expression and positive ceils in hippocampus tissues in intervention groups （Dis, Dz） were significantly decreased 3 d after surgery （P〈0.01, P〈0.05）. Conclusions Pretreatment with Dex can greatly reduce Caspase 3 and Bax protein expression and their positive cells in hippocampus tissues of mice and the improvement of POCD of mice is relevant to decrease expressions of caspase-3 and Bax.