Objective To investigate the protective effect and mechanism of Nimodipine on partial hepatectomized mice. Methods Thirty six healthy male C57BL/6 mice aged 18-20 months were randomly divided into 3 groups:control group (group C, n=12), without any special treatment; the surgery group (group S, n=12), with partial hepatectomy after anesthesia in mice; Nimodipine group (group Nimo, n = 12), the mice in group Nimo and group S were in the same operation, intraperitoneal injection of Nimodipine was started 1 day before surgery, mice were sacrificed at 3 days after surgery in each group, and hippocampus were moved quickly. T-maze assay was used to detect the ability of learning and memory of the experimental mice 3 days after surgery; and Nissel staining and transmission electron mi-croscopy was used to observe the change of hippocampal neuron survival quantity and ultrastructure in experimental mice; immunohistochemical method was used to detect the expression of Fas and FasL protein in the hippocampus of experimental mice. Results Compared with group C, the cognitive function of group S declined significantly on three days after surgery (P< 0.05); compared with the group S, group Nimo could improve the cognitive function on three days after surgery (P<0.05). Nissel staining showed that the quantities of hippocampal neurons increased significantly on 3 days after surgery in group Nimo; the transmission electron microscopy showed there was a mild ultrastructure change of hippocampal tissues on three days after surgery in group Nimo. The expression of Fas and FasL in hippocam-pal tissues of mice in group Nimo showed a decrease on three days after surgery compared with group S (P< 0.01). Conclusion Nimodipine can improve postoperative cognitive function by inhibiting the hippocampal neuron apoptosis mediated by Fas/FasL in aged mice.%目的:探讨尼莫地平对小鼠肝部分切除术后认知功能损伤的保护作用及作用机制。方法将36只18~20月龄健康雄性C57BL/6小鼠随机分为三组:对照组(C组,n =12),不做任何特殊处理;手术组(S组,n =12),小鼠在麻醉后行肝部分切除术;尼莫地平组(Nimo组,n =12),手术与S组相同,并于术前1 d开始腹腔注射尼莫地平。每组于术后3d处死实验小鼠,迅速获取海马组织。 T迷宫实验检测实验小鼠术后3d的学习和记忆能力;Nissel染色及透射电镜观察实验小鼠海马神经元存活的数量及超微结构改变;免疫组织化学方法检测实验小鼠海马Fas和FasL的蛋白表达。结果与C组比较,S组小鼠认知功能术后3 d明显下降(P<0.05);与S组比较,Nimo组可改善小鼠术后3 d的认知功能(P<0.05)。 Nissel染色可见Nimo组术后3 d小鼠海马神经元存活数量较S组明显增多;透射电镜下可见Nimo组术后3 d小鼠海马组织的超微结构改变较S组明显减轻。Nimo组术后3 d小鼠海马组织Fas和FasL表达较S组减少(P<0.01)。结论尼莫地平可通过抑制Fas/FasL介导的海马神经元凋亡而改善老龄小鼠的术后认知功能。
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