目的 观察盐酸右美托咪定对术后大鼠认知功能和海马区炎症反应的影响,探讨P2X7 受体在其中的作用机制。方法 成年雄性SD大鼠60只,随机分为3组：对照组(A组,n=20)、手术组(B组,n=20)、右美组(C组,n=20),B组和C组大鼠在腹腔注射2%戊巴比妥钠(50mg/kg)后施行脾切除术,A组大鼠仅仅开腹后关腹缝合,不进行脾切除术。C组在手术前进行尾静脉穿刺,于麻醉后经尾静脉给予右美托咪定初始计量10μg/kg (超过1min),随后以10μg/kg/h的速度输注；B组尾静脉穿刺后输注同等体积的生理盐水。手术结束后2周,在各组存活大鼠中随机选取 10只大鼠行 Morris 水迷宫实验观察认知功能的变化,使用酶联免疫吸附( ELISA) 法检测大鼠海马组织中IL-1β、TNF-α浓度,Western blot 法检测海马组织中 P2X7 的表达。 结果 与A组相比,B组大鼠找到水下平台的潜伏期明显延长,空间探索实验中跨越原平台次数明显减少,海马区IL-1β、TNF-α含量增高,P2X7表达明显上调,差异具有统计学意义(P<0.05)。与B组相比,C组大鼠找到水下平台的潜伏期明显延长,跨越原平台次数明显减少,海马区IL-1β、TNF-α含量增高,P2X7表达明显上调,差异具有统计学意义(P<0.05)。A组与C组大鼠相比,各项指标差异无统计学意义(P>0.05)。结论 盐酸右美托咪定可改善手术后引起的认知功能障碍,可能与盐酸右美托咪定抑制 P2X7 受体活性,降低海马区炎症反应有关。

Objective To observe the effects of dexmedetomidine hydrochloride on cognitive function and inflammatory response in hippocampus in postoperative rats, and to explore the mechanism of P2X7 receptors. Methods Eighty Elderly SD rats were randomly divided into a control group (group A,n=20),surgery group (group B,n=20) and dexmedetomidine group (group C,n=20). Splenectomy was performed in group B and group C after intraperitoneal injection of 2% pentobarbital sodium (50mg/kg) . The rats in group A underwent only laparotomy followed by abdominal closure without splenectomy.Group C underwent caudal vein puncture before operation. After anesthesia, dexmedetomidine was given in the caudal vein for an initial dose of 10 us g/kg over 1min, and continued infusion of 10 us g/kg/h.Group B was injected with the same volume of normal saline after caudal vein puncture.The Morris water maze behavior examination water was used to observe the changes of cognitive function in rats in the following 2 weeks after operation. The concentrations of IL-1β and TNF-α in rat hippocampus were detected by enzyme-linked immunosorbent assay (ELISA). The the expression of P2X7 receptors in hippocampus was detected by Western blot. Results Compared with group A, the incubation period of rats in group B to find the underwater platform was significantly prolonged, the frequency of crossing the original platform was significantly reduced in the space exploration experiment, the content of il-1 beta and tnf-alpha in the hippocampus was increased, and the expression of P2X7 was significantly up-regulated, with statistically significant differences (P<0.05).Compared with group B, the escape latency of the group C was shortened and the exploration time was prolonged,The levels of IL-1β and TNF-α in the hippocampus of the A group were significantly higher than group B,the expression of P2X7 receptors was significantly decreased in the group B(P< 0.05). Compared with rats in group A and group C, there was no statistically significant difference in various indicators (P>0.05).Conclusion Dexmedetomidine hydrochloride can improve postoperative cognitive dysfunction. The mechanism may be related to the activitySsuppression of P2X7 receptors by dexmedetomidine hydrochloride and the reduction of inflammatory response in hippocampus.

右美托咪定降低脑内胰岛素抵抗治疗POCD的基础研究