右美托咪定对术后老龄小鼠海马组织白介素1β和肿瘤坏死因子α表达的影响

Effects of dexmedetomidine on expressions of IL-1 β and TNF-α in hippocampus tissues of aged mice after surgery

目的探讨右美托咪定对手术创伤后老龄小鼠海马组织白介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)表达以及术后认知功能障碍(POCD)的影响。方法将105只老龄昆明小鼠随机分为4组。空白对照组(n=15):不实施麻醉和手术;麻醉药物组(n=30):腹腔注射氯胺酮100 mg/kg,持续吸入异氟醚60 min;麻醉药物+手术组(n=30):给予复合麻醉药物后实施剖腹探查脾切除手术;右美托咪定干预组(n=30):术前30 min各取15只小鼠分别给予右美托咪定15、25μg/kg腹腔内注射。术后第1日、第3日行Y迷宫实验(右美托咪定干预组在术后第3日进行),记录各组所需的训练次数;荧光定量PCR和Western blotting检测海马组织IL-1β、TNF-αmRNA及蛋白的表达。结果与空白对照组比较,麻醉药物组术后第1日训练次数增多(P<0.05),术后第3日恢复正常(P>0.05),麻醉药物+手术组术后第1日、第3日训练次数增多(P<0.01,P<0.05);术后第3日,右美托咪定15、25μg/kg干预组与空白对照组比较,差异均无统计学意义(P>0.05)。与空白对照组比较,麻醉药物+手术组术后第1日、第3日IL-1β、TNF-αmRNA及蛋白的表达量均显著升高(P<0.05或P<0.01);麻醉药物组术后第1日、第3日及右美托咪定干预组术后第3日IL-1β、TNF-αmRNA及蛋白的表达量与空白对照组比较,差异无统计学意义(P>0.05)。结论右美托咪定预处理能降低小鼠海马组织IL-1β、TNF-αmRNA及蛋白的表达,其改善小鼠POCD的作用与抑制海马炎症反应有关。

Objective To explore the effects of dexmedetomidine on expressions of IL-1 β and TNF-α in hippocampus tissues of aged mice after surgery and postoperative cognitive decline（ POCD）. Methods A total of105 aged Kunming mice were randomly divided into 4 groups, i. e. control group（ n = 15） that received no anesthesia and surgery, anesthesia group（ n = 30） that received consecutive isoflurane inhalation for 60 min and intraperitoneal injection of ketamine of 100 mg / kg, splenectomized group（ n = 30） that underwent splenectomy after anesthesia, intervention group（ n = 30） that received intraperitoneal injection of dexmedetomidine of 15 and 25 μg /kg（ 15 mice for each dose） 30 min before anesthesia and surgery. Y-maze experiments were conducted 1 d and 3 d after surgery（ Y-maze experiments were conducted 3 d after surgery for the intervention group）. The trial numbers of each group were recorded. The mRNA and protein expressions of IL-1β and TNF-α in hippocampus tissues weredetected by the qRT-PCR and Western blotting. Results The trial number of the anesthesia group was more than that of the control group 1 d after surgery（ P〈0. 05） and was back to normal 3 d after surgery（ P〉0. 05）. The trial number of the splenectomized group was more than that of the control group 1 d and 3 d after surgery（ P〈0. 01, P〈0. 05）. The differences of the intervention group and control group 3 d after surgery were not statistically significant（ P〉0. 05）. Compared with the control group, the mRNA and protein expressions of IL-1β and TNF-α of the splenectomized group significantly increased 1 d and 3 d after surgery（ P〈0. 05 or P〈0. 01）, and the differences of the mRNA and protein expressions of IL-1β and TNF-α of the anesthesia group（ 1 d and 3 d after surgery）, intervention group（ 3 d after surgery）, and control group were not statistically significant（ P〉0. 05）.Conclusion Pretreatment with dexmedetomidine can decrease the mRNA and protein expressions of IL-1β and TNF-α in hippocampus tissues of mice. The improvement of POCD of mice is relevant to the inhibition of inflammation responses of hippocampus.