摘要
目的观察齐拉西酮早期干预对改良单次延长应激(single prolonged stress and foot shock,SPS&S)模型大鼠行为的改善作用及大脑磷酸化细胞外信号调节激酶(phosphorylatedextracellularsignal-reg-ulated protein kinase,pERK1/2)表达的影响。方法24只SD大鼠随机分为对照组、模型组、齐拉西酮组以及齐拉西酮+U0126组,每组6只。对照组正常饲养;模型组为SPS&S处理组;齐拉西酮组为SPS&S造模结束后,每天灌胃齐拉西酮(2.5ms/kg),连续7d;齐拉西酮+U0126组为SPS&S造模结束后,连续7d给予齐拉西酮,并在每次齐拉西酮灌胃后0.5h,腹腔注射U0126(MEK1/2抑制剂)(0.5ms/kg)。各组在处理结束24h后,采用旷场和高架十字迷宫检测大鼠行为表现,并且在行为实验完成后处死大鼠,以蛋白质印迹法(Westernblot)检测大脑pERK1/2的表达水平。结果在旷场实验中,模型组大鼠水平活动度,中央活动次数[分别为(76.23±54.76)cm,(4.60±1.14)次]低于对照组[分别为(343.77±74.22)cm,(12.404-3.36)次]和齐拉西酮组[分别为(274.98÷83.56)cm,(12.00±2.92)次],差异有统计学意义(均P〈0.01),而与齐拉西酮+U0126组[分别为(138.14±41.98)cm,(5.00±1.58)次]相比,差异无统计学意义(均P〉0.05)。在高架十字测试中,各处理组在大鼠开臂进入次数和停留时间上的差异性与旷场实验的结果一致。Westernblot结果显示,模型组pERK1/2的表达水平明显低于对照组和齐拉西酮组,差异有统计学意义(均P〈0.01)。结论齐拉西酮能改善PTSD动物的焦虑样行为,而且这种作用可能是通过上调pERK1/2的表达实现的。
Objective To investigate the effects of ziprasidone on the behavior and the expression of pERK1/2 in posttraumatic stress disorder(PTSD) model rats. Methods 24 adult male SD rats weighing (200 ± 20 ) g were randomly divided into four groups (n= 6 ) : control group, single prolonged stress and foot shock(SPS&S) group,ziprasidone group and ziprasidone + U0126 group. The fear response to environment, high alertness, and anxiety & depression behavior of rats were tested by the open field, elevated plus-maze, and the expression of pERK1/2 was measured by Western blot. Results In open field test( OFT), the SPS&S group ( (76.23 ± 54.76) cm for horizontal motion distance, (4.60 ± 1.14 )for the number of entering central region) showed significant difference compared with control group( (343.77± 74.22) cm, ( 12. 40 ±3.36) ) or ziprasidone group( (274.98 ± 83.56 ) cm, ( 12.00 ± 2.92) ) (P 〈 0.01 ), but showed no significant difference with ziprasidone + U0126 group ( ( 138.14 ± 41.98) cm, (5.00 ± 1.58 ) ) (P 〉 0.05 ). The results of elevated plus maze ( EPM ) were in accordance with the results of OFT. The expression of pERK1/2 in SPS&S group and ziprasidone + U0126 group showed significant decrease when compared with control group or ziprasidone group (P 〈 0.01 ). Conclusion Ziprasidone can obviously improve fear response to environment, high aherness and anxiety & depression behavior of rats, and these effects of ziprasidone may be carried out by up-regulation the expression of pERK1/2.
出处
《中华行为医学与脑科学杂志》
CAS
CSCD
北大核心
2012年第10期869-871,共3页
Chinese Journal of Behavioral Medicine and Brain Science
基金
国家自然科学基金项目(30870886)
关键词
齐拉西酮
创伤后应激障碍
磷酸化细胞外信号调节激酶
大鼠
Ziprasidone
Posttraumatic stress disorder
Phosphorylated extracellular signal-regulated- protein kinase
Rat