氯胺酮复合异丙酚麻醉对抑郁大鼠电休克后海马谷氨酸受体亚基1和亚基2的影响

摘要

目的：评价小剂量氯胺酮复合异丙酚麻醉对抑郁大鼠电休克（electroconvulsive therapy，ECT）后海马谷氨酸受体亚基1（glutamate receptor subunit 1，GluR1）及亚基2（glutamate receptor subunit 2，GluR2）的影响。方法健康成年雄性SD大鼠32只，采用孤养与慢性轻度不可预见性应激（chronic unpredictable mild stress， CUMS）建立抑郁模型，建模成功后随机分为抑郁组（A组）、ECT组（B组）、ECT+异丙酚组（C组）和ECT+异丙酚+氯胺酮组（D组）4组，每组8只；另取8只正常大鼠作为对照组。对照组不做任何处理；A组腹腔注射生理盐水8 mL/kg后给予伪ECT处理；B、C、D组分别腹腔注射生理盐水8 mL/kg、异丙酚80 mg/kg、异丙酚80 mg/kg+氯胺酮10 mg/kg后行ECT处理，上述处理连续7 d。分别采用糖水偏好实验和Morris水迷宫实验评价大鼠抑郁状态和学习记忆功能，Western-blot及RT-PCR检测大鼠海马GluR1和GluR2及其mRNA表达。结果 ECT处理后， B、C、D组糖水偏好百分比变化均较A组和对照组明显，其中D组升高最为明显（均P<0.05）；B组逃避潜伏期延长且变化值与其他组均具有统计学差异，而D组逃避潜伏期缩短最为明显，其次为A组（均P<0.05）；B组空间探索时间缩短且变化值均大于其他组，D组空间探索时间延长最为明显（均P<0.05）。ECT处理后，B、C、D组GluR1表达较A组高，其中D组最高（均P<0.05）；GluR1 mRNA表达在组间无统计学差异B、C组GluR2及其mRNA表达较其余组低，其中B组最低（均P<0.05），A、D组和对照组间GluR2及其mRNA差异无统计学意义（P>0.05）。结论小剂量氯胺酮复合异丙酚麻醉在协同ECT抗抑郁效果的同时，能够更大程度地改善ECT后学习记忆功能，其机制可能与上调海马GluR1和GluR2表达相关。%Objective To explore the effect of low-dose ketamine combined with propofol anesthesia on expres⁃sion of glutamine receptor subunit 1 (GluR1) and 2 (GluR2) in the hippocampus of depressed rats after electroconvulsive therapy. Methods Healthy adult male Sprague-Dawley rats, weighing 200~250 g, were used in this study. Mental depres⁃sion was induced by chronic unpredictable mild stress. Thirty-two depressed rats were randomly divided into 4 groups (n=8): metal depression group (group A), ECT group (group B), ECT+propofol group (group C) and ECT+propofol+ket⁃amine group (group D). Eight normal rats served as control group. Control group received no treatment. Group A received intraperitoneal injection of normal saline 8 mL/kg plus sham ECT. Group B, C and D received ECT once a day for 7 con⁃secutive days following intraperitoneal injection of normal saline 8 mL/kg, propofol 80 mg/kg and propofol 80 mg/kg +ketamine 10mg/kg, respectively. Sucrose preference test and Morris water maze were performed to assess depressed be⁃havior and learning and memory function, respectively. RT-PCR and Western-blot assay were used to detect the expres⁃sion of GluR1 , GluR2 and their mRNA expression. Results After ECT, compared with control group and group A, changes of SPP in group B, C and D were obvious. The change of SPP in group D was much higher than all other groups (P<0.05). Rats in group B showed prolonged escape latency and shortened space exploration time, which were significantly different from all other groups (P<0.05). Rats in group D showed the most shortened escape latency and prolonged space exploration time (P<0.05). The expression of GluR1 was significantly increased in group B, C and D compared with group A (P<0.05). The expression of GluR2 and mRNA was significantly decreased in group B and C (P<0.05). The difference in GluR2 and mRNA expression was not significant among group A, D and control group (P>0.05). Conclusion Low-dose ketamine combined with propofol anesthesia exert effective antidepressive action and improve learning and memory function of depressed rats after electroconvulsive therapy. The beneficial effects of the ketamine combined with propofol anesthesia may be related to up-regulation expression of GluR1 and GluR2 in hippocampus.