CAJ | 학술논문

目的评价右美托咪定预防大鼠创伤后应激障碍(PTSD)的效果及其对海马细胞外信号调节激酶(ERK)活性及活动调节骨架蛋白(ARC)表达的影响.方法成年雄性SD大鼠68只,体重250～280 g,采用随机数字表法,将大鼠分为4组(n=17)∶生理盐水组(NS组)、右美托咪定0.3 μg/kg组(D1组)、右美托咪定3.0μg/kg组(D2组)和右美托咪定9.0μg/kg组(D3组).于PTSD模型制备前30 min,NS组腹腔注射生理盐水2 ml,D1组、D2组和D3组分别腹腔注射右美托咪定0.3、3.0和9.0μg/kg.采用应激增强恐惧学习法制备PTSD模型.于模型制备第1天A室电击处理后15 min时采用Western blot法检测海马ERK、磷酸化ERK(p-ERK)的表达水平；第1天A室电击处理后30 min时采用Western blot法检测海马ARC的表达水平.结果与模型制备第2天比较,3组大鼠模型制备第3天木僵率升高(P＜0.05)；与NS组比较,D2组和D3组模型制备第3天木僵率均下降,海马p-ERK和ARC表达降低(P＜0.05),D1组上述指标差异无统计学意义(P＞0.05)；D2组和D3组上述指标比较差异无统计学意义(P＞0.05).4组大鼠海马ERK表达差异无统计学意义(P＞0.05).结论右美托咪定对大鼠PTSD有一定预防作用,且与剂量有关,该作用机制与抑制海马ERK活性,下调ARC表达有关.
목적 평개우미탁미정예방대서창상후응격장애(PTSD)적효과급기대해마세포외신호조절격매(ERK)활성급활동조절골가단백(ARC)표체적영향.방법 성년웅성SD대서68지,체중250～280 g,채용수궤수자표법,장대서분위4조(n=17)∶생리염수조(NS조)、우미탁미정0.3 μg/kg조(D1조)、우미탁미정3.0μg/kg조(D2조)화우미탁미정9.0μg/kg조(D3조).우PTSD모형제비전30 min,NS조복강주사생리염수2 ml,D1조、D2조화D3조분별복강주사우미탁미정0.3、3.0화9.0μg/kg.채용응격증강공구학습법제비PTSD모형.우모형제비제1천A실전격처리후15 min시채용Western blot법검측해마ERK、린산화ERK(p-ERK)적표체수평；제1천A실전격처리후30 min시채용Western blot법검측해마ARC적표체수평.결과 여모형제비제2천비교,3조대서모형제비제3천목강솔승고(P＜0.05)；여NS조비교,D2조화D3조모형제비제3천목강솔균하강,해마p-ERK화ARC표체강저(P＜0.05),D1조상술지표차이무통계학의의(P＞0.05)；D2조화D3조상술지표비교차이무통계학의의(P＞0.05).4조대서해마ERK표체차이무통계학의의(P＞0.05).결론 우미탁미정대대서PTSD유일정예방작용,차여제량유관,해작용궤제여억제해마ERK활성,하조ARC표체유관.
Objective To evaluate the efficacy of dexmedetomidine in prevention of posttraumatic stress disorder (PTSD) and effects of dexmedetomidine on extracellular signal-regulated kinase (ERK) activity and activity-regulated-cytoskeletal protein (ARC) expression in hippocampus in rats.Methods Sixty-eight adult male Sprague-Dawley rats,weighing 250-280 g,were randomly divided into 4 groups (n =17 each):normal saline group (group NS) and dexmedetomidine 0.3,3.0 and 9.0 μg/kg groups (groups D1,D2,D3).An animal model of PTSD,stress-enhanced fear learning (lasting for 3 days),was made.In group NS normal saline 2 ml was injected intraperitioneally at 30 min before stress-enhanced fear learning,while in groups D1,D2 and D3,dexmedetomidine 0.3,3.0 and 9.0 μg/kg were injected intraperitioneally,respectively,at 30 min before stress-enhanced fear learning.The expression of ERK and phosphorylated ERK (p-ERK) in hippocampus was measured by Western blot at 15 min after exposure to electrical shocks in one environment (Context A) on 1st day the model was established.The expression of ARC in hippocampus was detected by Western blot at 30 min after exposure to electrical shocks in Context A on 1 st day the model was established.Results The freezing rate was significantly higher on 3rd day than on 2nd day in each group (P ＜ 0.05).Compared with group NS,the freezing rate was significantly decreased and the expression of p-ERK and ARC was down-regulated on 3rd day in groups D2 and D3 (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group D1 (P ＞ 0.05).There was no significant difference in the paramenters mentioned above between groups D2 and D3 (P ＞ 0.05).There was no significant difference in the expression of ERK between the four groups (P ＞ 0.05).Conclusion Dexmedetomidine prevents PTSD to some extent in a dose-dependent manner and inhibition of ERK activity and decrease in ARC expression in hippocampus are involved in the mechanism.