国际麻醉学与复苏杂志   2016, Issue (5): 9-9
    
右美托咪定对术后老龄小鼠海马组织caspase-3、Bax表达的影响
钱晓岚1()
1.河南省直第三人民医院麻醉科
Effects of dexmedetomidine on postoperative expressions of caspase-3 and Bax in hippocampus tissues of aged mice
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摘要:

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(postoperative cognitive decline, POCD)的影响。 方法 健康老龄昆明小鼠105只,13~15月龄,体重45~55 g。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30 min各取15只小鼠分别给予Dex 15、25 μg/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); Western blot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]训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, P<0.05); D15、D25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<0.05)。 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。

关键词: 右美托咪定; 老龄; caspase-3; Bax; 术后认知功能障碍; 小鼠
Abstract:

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 15 μg/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?蛳behavioral differences(Y?蛳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?蛳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(D15, D25 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, D25) 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 cells in hippocampus tissues in intervention groups(D15, D25) 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.

Key words: Dexmedetomidine; Aged or elderly; Caspase 3; Bax; Postoperative cognitive dysfunction; Mice