CAJ | 학술논문

目的评价尼莫地平预先给药对老龄大鼠术后认知功能障碍的影响.方法健康雄性SD大鼠90只,18月龄,体重400～500 g,采用随机数字表法分为3组(n=30):尼莫地平对照组(N组)、手术组(S组)和尼莫地平+手术组(N+S组).N组和N+S组腹腔注射尼莫地平1 mg/kg、S组腹腔注射等容量生理盐水30 min后,N组大鼠吸入纯氧2h,S组和N+S组大鼠吸入1.8％异氟醚麻醉下行脾脏切除术.于术前1d、术后1、3和7d时行Morris水迷宫实验;并于术前1d、术后1和7d时Morris水迷宫实验结束后随机取10只大鼠处死,取海马组织,采用流式细胞术测定海马神经元凋亡率、胞浆Ca2+浓度([Ca2+]i);采用RT-PCR法检测海马Bcl-2、Bax的mRNA表达;透射电镜下观察大鼠海马神经元超微结构.结果与术前1d时比较,S组和N+S组术后各时点逃避潜伏期延长,原平台穿越次数减少,海马神经元凋亡率、[Ca2+]i升高,Bcl-2 mRNA表达下调,Bax mRNA表达上调,Bax/Bcl-2 mRNA比值升高(P＜0.05),N组给药后各时点逃避潜伏期、原平台穿越次数、海马神经元凋亡率、[Ca2+]i、Bcl-2和Bax的mRNA表达差异无统计学意义(P＞0.05);与S组比较,N+S组术后逃避潜伏期缩短和原平台穿越次数增多,海马神经元凋亡率、胞浆[Ca2+]i降低,Bcl-2 mRNA表达上调,BaxmRNA表达下调,Bax/Bcl-2 mRNA比值降低(P＜0.05).S组和N+S组海马神经元电镜下出现病理学损伤,S组损伤重于N+S组.结论尼莫地平预先给药可降低老龄大鼠术后认知功能障碍的发生,其机制可能与抑制钙超载引起的海马神经元凋亡有关.
목적 평개니막지평예선급약대노령대서술후인지공능장애적영향.방법 건강웅성SD대서90지,18월령,체중400～500 g,채용수궤수자표법분위3조(n=30):니막지평대조조(N조)、수술조(S조)화니막지평+수술조(N+S조).N조화N+S조복강주사니막지평1 mg/kg、S조복강주사등용량생리염수30 min후,N조대서흡입순양2h,S조화N+S조대서흡입1.8％이불미마취하행비장절제술.우술전1d、술후1、3화7d시행Morris수미궁실험;병우술전1d、술후1화7d시Morris수미궁실험결속후수궤취10지대서처사,취해마조직,채용류식세포술측정해마신경원조망솔、포장Ca2+농도([Ca2+]i);채용RT-PCR법검측해마Bcl-2、Bax적mRNA표체;투사전경하관찰대서해마신경원초미결구.결과 여술전1d시비교,S조화N+S조술후각시점도피잠복기연장,원평태천월차수감소,해마신경원조망솔、[Ca2+]i승고,Bcl-2 mRNA표체하조,Bax mRNA표체상조,Bax/Bcl-2 mRNA비치승고(P＜0.05),N조급약후각시점도피잠복기、원평태천월차수、해마신경원조망솔、[Ca2+]i、Bcl-2화Bax적mRNA표체차이무통계학의의(P＞0.05);여S조비교,N+S조술후도피잠복기축단화원평태천월차수증다,해마신경원조망솔、포장[Ca2+]i강저,Bcl-2 mRNA표체상조,BaxmRNA표체하조,Bax/Bcl-2 mRNA비치강저(P＜0.05).S조화N+S조해마신경원전경하출현병이학손상,S조손상중우N+S조.결론 니막지평예선급약가강저노령대서술후인지공능장애적발생,기궤제가능여억제개초재인기적해마신경원조망유관.
Objective To evaluate the effect of preconditioning with nimodipine on postoperative cognitive dys function of aged rats.Methods Ninety healthy male Sprague-Dawley rats,aged 18 months,weighing 400-500 g,were randomly divided into 3 groups (n =30 each) using a random number table:nimodipine control group (group N),surgery group (group S),and nimodipine + surgery group (N+ S group).In N and N + S groups,nimodipine 1 mg/kg was intraperitoneally injected,while the equal volume of normal saline was given instead in S group.30 min later,group N inhaled pure oxygen for 2 h,and S and N + S groups inhaled 1.8 ％ isoflourane for 2 h when splenectomy was performed.Morris water maze test was performed on 1 day before operation and 1st,3rd and 7th days after operation.After the end of Morris water maze test at 1 day before operation and 1st and 7th days after operation,10 rats were sacrificed and brains were removed and hippocampi were isolated for determination of apoptosis in hippocampal neurons,intracellular [Ca2+] i in cytoplasm,and hippocampal Bcl-2 and Bax mRNA expression and for examination of ultrastructure of hippocampal neurons.Results Compared with the value before administration,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,apoptotic rate and [Ca2+]i were increased,Bcl-2 mRNA expression was down-regulated,and Bax mRNA expression and Bax/Bcl-2 mRNA ratio were up-regulated at each time point after operation in S and N + S groups,and no significant changes were found in the parameters mentioned above in N group.Compared with group S,the escape latency was significantly shortened,the frequency of crossing the original platform was inecreased,apoptotic rate and [Ca2+]i were decreased,Bcl-2 mRNA expression was up-regulated,and Bax mRNA expression was down-regulated at each time point after operation in group N + S.Pathological changes were found in S and N + S groups and the damage was severer in S group than in N + S group.Conclusion Nimodepine preconditioning can prevent postoperative cognitive dysfunction of aged rats,and inhibition of calcium overloadinduced apoptosis in hippocampal neurons may be involved in the mechanism.