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  • 滕清宇,蔡林林,李玮伟,袁红斌,徐海涛.R-α-甲基组胺改善异氟烷导致的发育期大鼠神经元凋亡及记忆损害[J].第二军医大学学报,2017,38(8):1023-1027    [点击复制]
  • TENG Qing-yu,CAI Lin-lin,LI Wei-wei,YUAN Hong-bin,XU Hai-tao.R-(-)-α-methylhistamine ameliorates isoflurane-induced neuronal apoptosis and memory impairment in developing rats[J].Acad J Sec Mil Med Univ,2017,38(8):1023-1027   [点击复制]
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R-α-甲基组胺改善异氟烷导致的发育期大鼠神经元凋亡及记忆损害
滕清宇,蔡林林,李玮伟,袁红斌,徐海涛*
0
(第二军医大学长征医院麻醉科, 上海 200003
*通信作者)
摘要:
目的 探讨R-α-甲基组胺(RAMH)对异氟烷导致的发育期大鼠神经元凋亡及记忆损害的保护作用。方法 将28只6~7 d SD大鼠随机均分为4组:对照(CON)组腹腔注射5%葡萄糖(0.1 mL/10 g);异氟烷暴露模型(ISO)组腹腔注射5%葡萄糖(0.1 mL/10 g)后,吸入1.6%的异氟烷持续6 h;RAMH组腹腔注射RAMH (10 mg/kg);异氟烷暴露联合RAMH处理(RAMH+ISO)组,腹腔注射RAMH (10 mg/kg)30 min后吸入1.6%的异氟烷持续6 h。应用水迷宫实验观察大鼠学习记忆能力,免疫荧光技术检测大鼠海马神经细胞凋亡,蛋白质印迹法检测大鼠海马中p53蛋白表达。结果 在水迷宫实验中,ISO组大鼠在目标象限的时间短于CON组(n=7,P<0.01);RAMH+ISO组大鼠在目标象限的时间长于ISO组(n=7,P<0.05)。与CON组相比,ISO组大鼠海马神经细胞凋亡增加(n=5,P<0.01);而RAMH+ISO组凋亡细胞数量少于ISO组(n=5,P<0.01)。与CON组相比,ISO组大鼠海马中p53蛋白表达增加(n=6,P<0.01);而RAMH+ISO组p53蛋白表达低于ISO组(n=6,P<0.01)。结论 RAMH可减轻异氟烷引起的发育期大鼠海马神经元凋亡及记忆损害。
关键词:  异氟烷  R-α-甲基组胺  生长和发育  细胞凋亡  记忆障碍
DOI:10.16781/j.0258-879x.2017.08.1023
投稿时间:2017-03-23修订日期:2017-06-24
基金项目:国家自然科学基金(81400895).
R-(-)-α-methylhistamine ameliorates isoflurane-induced neuronal apoptosis and memory impairment in developing rats
TENG Qing-yu,CAI Lin-lin,LI Wei-wei,YUAN Hong-bin,XU Hai-tao*
(Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
*Corresponding author)
Abstract:
Objective To explore the effect of R-(-)-α-methylhistamine (RAMH) on the isoflurane exposure induced neuronal apoptosis and memory impairment in the developing rats. Methods Twenty-eight 6-7 days SD rats were randomly divided into four groups:control (CON) group (intraperitoneal injection of 5% glucose[0.1 mL/10 g], isoflurane (ISO) group (intraperitoneal injection of 5% glucose[0.1 mL/10 g] and then exposure to 1.6% ISO for 6 hours), RAMH group (intraperitoneal injection of RAMH[10 mg/kg], and RAMH+ISO group (after intraperitoneal injection of RAMH[10 mg/kg] for 30 min, then exposure to 1.6% ISO for 6 hours). Morris water maze test was employed to investigate the learning and memory ability. Immunofluorescence and Western blotting were employed to determine the neuronal apoptosis and p53 expression in the hippocampus of rats, respectively. Results Morris water maze test showed that the time in the target quadrant of ISO group was significantly shorter than that of CON group (n=7, P<0.01), while the time of RAMH+ISO group was significantly longer than the ISO group (n=7, P<0.05). The number of apoptotic neurons in hippocampus in the ISO group was significantly increased compared with either the CON group or the RAMH+ISO group (n=5, both P<0.01). Compared with the CON group, the expression of p53 protein in hippocampus was significantly increased in the ISO group (n=6, P<0.01), while p53 expression in the RAMH+ISO group was significantly lower than that in the ISO group (n=6, P<0.01). Conclusion RAMH can ameliorate ISO exposure induced neuronal apoptosis and memory impairment in the developing rat.
Key words:  isoflurane  R-(-)-α-methylhistamine  growth and development  apoptosis  memory disorders