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丙泊酚对电休克应激大鼠海马神经元型一氧化氮合酶及其羧基端 PDZ 配体表达的影响。

Effects of propofol on expression of hippocampal neuronal nitric oxide synthase and carboxy-terminal PDZ ligand of neuronal nitric oxide synthase in stressed rats undergoing electroconvulsive shock.

机构信息

From the *Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University, and †Department of Anesthesiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

J ECT. 2013 Dec;29(4):297-302. doi: 10.1097/YCT.0b013e318290fa17.

Abstract

OBJECTIVES

This study aimed at investigating the effects of propofol on the expression of hippocampal neuronal nitric oxide synthase (nNOS) and carboxy-terminal PDZ ligand of nNOS (CAPON) in stressed rats after electroconvulsive shock (ECS).

METHODS

Sprague-Dawley rats were stressed repeatedly for 28 days to establish a stressed model. Forty stressed rats were randomly divided into 4 groups (n = 10 for each group): the stressed group (unapplied group), propofol group (applied with intraperitoneal injection of propofol 80 mg/kg for 7 days), ECS group (applied with ECS and intraperitoneal injection of normal saline 8 mL/kg), or propofol + ECS group (applied with ECS and intraperitoneal injection of propofol 80 mg/kg). Sucrose preference test, open-field test, and Morris water maze were used to assess behavioral changes. Immunohistochemistry was carried out to measure the expression of nNOS and CAPON in hippocampal CA1, CA3, and DG areas.

RESULTS

Rats in the ECS and propofol + ECS groups had higher sucrose preference percentages and open-field scores when compared with the stressed group. Rats in the ECS group exhibited longer escape latency, shorter space exploration time, up-regulated expression of nNOS, down-regulated expression of CAPON, and increased ratio of nNOS/CAPON in hippocampus. Compared with the ECS group, the propofol + ECS group exhibited shorter escape latency, longer space exploration time, down-regulated expression of nNOS, up-regulated expression of CAPON in hippocampus, and lower nNOS/CAPON values.

CONCLUSIONS

Propofol may alleviate ECS-induced impairment of learning and memory in stressed rats by inhibiting excessive expression of nNOS and enhancing the expression of CAPON to maintain the balance between nNOS and CAPON in hippocampus.

摘要

目的

本研究旨在探讨异丙酚对电休克后应激大鼠海马神经元型一氧化氮合酶(nNOS)和 nNOS 羧基末端 PDZ 配体(CAPON)表达的影响。

方法

采用重复应激 28 天的方法建立应激模型。将 40 只应激大鼠随机分为 4 组(每组 10 只):应激组(未处理组)、异丙酚组(腹腔注射异丙酚 80mg/kg,连续 7 天)、电休克组(电休克,腹腔注射生理盐水 8mL/kg)和异丙酚+电休克组(电休克,腹腔注射异丙酚 80mg/kg)。采用糖水偏好实验、旷场实验和 Morris 水迷宫实验评估行为变化,免疫组织化学法检测海马 CA1、CA3 和 DG 区 nNOS 和 CAPON 的表达。

结果

与应激组相比,电休克组和异丙酚+电休克组大鼠的糖水偏好百分比和旷场得分均升高。电休克组大鼠逃避潜伏期延长,空间探索时间缩短,nNOS 表达上调,CAPON 表达下调,海马 nNOS/CAPON 比值升高。与电休克组相比,异丙酚+电休克组大鼠逃避潜伏期缩短,空间探索时间延长,nNOS 表达下调,CAPON 表达上调,海马 nNOS/CAPON 值降低。

结论

异丙酚可能通过抑制 nNOS 的过度表达,增强 CAPON 的表达,维持海马 nNOS 和 CAPON 之间的平衡,从而减轻电休克引起的应激大鼠学习记忆损伤。

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