文章摘要
尼莫地平复合7.5%高渗盐水对七氟醚诱导老龄大鼠海马神经元凋亡的影响
Effects of nimodipine combined with 7.5% hypertonic saline on sevoflurane-induced apoptosis of hippocampal neuron in aged rats
  
DOI:10.12089/jca.2017.12.1215
中文关键词: 尼莫地平  高渗盐水  老龄大鼠  神经元凋亡
英文关键词: Nimodipine  Hypertonic saline  Aged rats  Neuronal apoptosis
基金项目:国家自然科学基金面上项目(81771134); 河北省政府资助临床优秀人才培养和基础课题研究项目(361005)
作者单位E-mail
张琦 050051,石家庄市, 河北医科大学第三医院麻醉科  
李亚南 050051,石家庄市, 河北医科大学第三医院麻醉科  
郭鹏 050051,石家庄市, 河北医科大学第三医院麻醉科  
信茜 050051,石家庄市, 河北医科大学第三医院麻醉科  
霍树平 050051,石家庄市, 河北医科大学第三医院麻醉科  
王秋筠 050051,石家庄市, 河北医科大学第三医院麻醉科 13933178001@163.com 
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中文摘要:
      
目的 探讨尼莫地平复合7.5%高渗盐水对七氟醚诱导老龄大鼠海马神经元凋亡的影响。
方法 健康雄性Wistar大鼠96只, 18月龄, 体重450~500 g,采用随机数字表法将其分为四组(n=24): 对照组(C组)、尼莫地平组(N组)、高渗盐水组(HS组)和尼莫地平+高渗盐水组(NHS组)。C组腹腔和尾静脉注射生理盐水; N组腹腔注射尼莫地平1 mg/kg, 尾静脉注射生理盐水; HS组尾静脉注射7.5%高渗盐水4 ml/kg, 腹腔注射生理盐水; NHS组腹腔注射尼莫地平1 mg/kg, 尾静脉注射7.5%高渗盐水4 ml/kg。30 min后四组大鼠吸入3%七氟醚2 h。于麻醉前1 d、麻醉后1、3、7 d行Morris水迷宫实验, 实验结束后每组随机处死8只大鼠, 取海马组织, 采用流式细胞术测定海马神经元凋亡率和胞浆钙离子浓度; 采用RT PCR法测定海马Bcl 2、Bax的mRNA表达量。
结果 与C组比较, N、HS、NHS组大鼠麻醉后1、3、7 d逃避潜伏期明显缩短, 穿越原平台次数明显增加, 麻醉后1、7 d海马神经元凋亡率和胞浆钙离子浓度明显减低, Bcl-2 mRNA表达量明显上调, Bax mRNA表达量明显下调, Bax/Bcl-2比值明显降低(P<0.05); 与NHS组比较, N和HS组大鼠麻醉后1、3、7 d逃避潜伏期明显延长, 穿越原平台次数明显减少, 麻醉后1、7 d海马神经元凋亡率和胞浆钙离子浓度明显增高, Bcl-2 mRNA表达量明显下调,Bax mRNA表达量明显上调,Bax/Bcl-2比值明显升高(P<0.05)。
结论 尼莫地平复合7.5%高渗盐水可抑制钙超载, 降低七氟醚诱导老龄大鼠海马神经元凋亡率, 且其作用优于单独给药。
英文摘要:
      
Objective To evaluate the effects of nimodipine combined with 7.5% hypertonic saline (HS) on sevoflurane-induced apoptosis of hippocampal neuron in aged rats.
Methods Ninety-six healthy male Wistar rats aged 18 months and weighing 450-500 g were randomly assigned into 4 groups (n=24 each): group C, group N, group HS and group NHS. Group N received intraperitoneal injection of 1 mg/kg nimodipine and intravenous injection of normal saline, group HS received intravenous injection of 4 ml/kg 7.5% HS and intraperitoneal injection of normal saline, group NHS received intraperitoneal nimodipine and intravenous HS mentioned above and group C received normal saline. Thirty minutes later, 4 groups inhaled 3% sevoflurane for 2 hours. Morris water maze test was performed 1 day before anesthesia and 1, 3 and 7 days after anesthesia. Morris water maze test was carried out 1 day before anesthesia and 1 and 7 days after anesthesia, 8 rats were sacrificed and brains were removed. Hippocampal tissues were obtained for detection of apoptosis in hippocampal neurons, intracellular [Ca2+]i by flow cytometry and the measurement of Bcl-2 and Bax mRNA expression by RT-PCR.
Results Compared with group C, the escape latency, apoptotic rate, [Ca2+]i, Bax mRNA expression and Bax/Bcl-2 ratio were significantly decreased, the frequency of crossing the original platform and Bcl-2 mRNA expression increased in groups N, HS and NHS after anesthesia (P<0.05). Compared with group NHS, the escape latency, apoptotic rate, [Ca2+]i, Bax mRNA expression and Bax/Bcl-2 ratio were significantly increased, the frequency of crossing the original platform and Bcl-2 mRNA expression were decreased in groups N and HS after anesthesia (P<0.05).
Conclusion Nimodipine combined with 7.5%HS could reduce apoptosis rate of sevoflurane-induced hippocampal neuron by inhibiting calcium overload in aged rats, and it exerts better protective effects than single drug administration.
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