CAJ | 학술논문

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(phosphorylated extracellular signal-regulated 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( 2.5 mg/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)(0.5 mg/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(Western blot)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,(12.40±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.Western blot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.
목적 관찰제랍서동조기간예대개량단차연장응격(single prolonged stress and foot shock,SPS&S)모형대서행위적개선작용급대뇌린산화세포외신호조절격매(phosphorylated extracellular signal-regulated protein kinase,pERK1/2)표체적영향.방법 24지SD대서수궤분위대조조、모형조、제랍서동조이급제랍서동+ U0126조,매조6지.대조조정상사양；모형조위SPS&S처리조；제랍서동조위SPS&S조모결속후,매천관위제랍서동( 2.5 mg/kg),련속7d；제랍서동+U0126조위SPS&S조모결속후,련속7d급여제랍서동,병재매차제랍서동관위후0.5h,복강주사U0126(MEK1/2억제제)(0.5 mg/kg).각조재처리결속24h후,채용광장화고가십자미궁검측대서행위표현,병차재행위실험완성후처사대서,이단백질인적법(Western blot)검측대뇌pERK1/2적표체수평.결과 재광장실험중,모형조대서수평활동도,중앙활동차수[분별위(76.23±54.76) cm,(4.60±1.14)차]저우대조조[분별위(343.77±74.22) cm,(12.40±3.36)차]화제랍서동조[분별위(274.98±83.56) cm,(12.00±2.92)차],차이유통계학의의(균P＜0.01),이여제랍서동+U0126조[분별위(138.14±41.98)cm,(5.00±1.58)차]상비,차이무통계학의의(균P＞0.05).재고가십자측시중,각처리조재대서개비진입차수화정류시간상적차이성여광장실험적결과일치.Western blot결과현시,모형조pERK1/2적표체수평명현저우대조조화제랍서동조,차이유통계학의의(균P＜0.01).결론 제랍서동능개선PTSD동물적초필양행위,이차저충작용가능시통과상조pERK1/2적표체실현적.
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 alterness and anxiety & depression behavior of rats,and these effects of ziprasidone may be carried out by up-regulation the expression of pERK1/2.