摘要：
Objective It is to study the effect of oxymatrine on learning and memory ability after chronic cerebral ischemia in rats and to explore its possible mechanism. Methods 100 SD rats were randomly divided into sham operation group, model group, oxymatrine low dose group, oxymatrine medium dose group and oxymatrine high dose group, 20 rats in each group. Except for the sham operation group, the rat models of chronic cerebral ischemia were established by ligation of bilateral common carotid arteries. On the 2nd day after operation, the low, medium and high doses of oxymatrine groups were given intraperitoneal injection of oxymatrine 25 mg/ (kg · d) , 50 mg/ (kg · d) and 100 mg/ (kg · d) , respectively, 1time/d, continously treating for 7 days. On the 2nd day after the last injection, Morris water maze test and platform test were used to evaluate the learning and memory ability of the rats. Hematoxylin-Yinhong (HE) staining and TUNEL method were respectively used to observe the morphology and necrosis of hippocampal CA1 neurons. The expression of Bcl-2 and Bax protein in hippocampus was detected by immunohistochemistry. The activities of antioxidant enzymes [superoxide dismutase (SOD) , catalase (CAT) ] and content of malondialdehyde (MDA) in hippocampus were analyzed by biochemical analysis. Results In the water maze experiment, the escape latency and escape route of the oxymatrine medium and high dose groups were significantly shorter, and the number of crossing platforms was significantly higher than that of the model group (P ＜ 0. 05). In the platform test, the number of errors in the middle and high dose groups of oxymatrine was significantly lower, the total time of electric shock was significantly shorter than that in the model group (P ＜ 0. 05). The morphological changes and apoptosis of hippocampal CA1 neurons in the middle and high dose groups of oxymatrine were significantly less, the neuronal apoptosis index was significantly lower, the expression of Bcl-2 and the ratio of Bcl-2/Bax in the hippocampus were significantly higher, and the expression of Bax was significantly lower than those of the model group (P ＜0. 05). The activities of SOD and CAT in the hippocampus of rats in the middle and high dose groups of oxymatrine were significantly higher, and the MDA content was significantly lower than that of the model group (P ＜ 0. 05). Conclusion Oxymatrine can improve the learning and memory ability of rats with chronic cerebral ischemia. The mechanism may be related to the regulation of hippocampal apoptosis-related gene expression, inhibiting hippocampal neuronal apoptosis and increasing antioxidant enzyme activity and reducing oxidative stress injury.%目的 研究苦参素对大鼠慢性脑缺血后学习记忆能力的影响并探讨其可能的作用机制.方法 将100只SD大鼠随机分为假手术组、模型组、苦参素低剂量组、苦参素中剂量组、苦参素高剂量组, 每组20只.除假手术组外, 其余组采用结扎双侧颈总动脉的方法复制慢性脑缺血大鼠模型.术后第2天, 苦参素低、中、高剂量组分别给予苦参素25 mg/ (kg·d) 、50 mg/ (kg·d) 、100 mg/ (kg·d) ) 腹腔注射, 1次/d, 连续7 d.末次注射后第2天, 采用Morris水迷宫实验和跳台实验评价大鼠学习记忆能力, 通过苏木精-尹红 (HE) 染色、末端标记 (TUNEL) 法分别观察海马CA1区神经元形态及凋亡情况, 免疫组织化学法检测海马中Bcl-2、Bax蛋白表达情况, 生化分析海马组织中抗氧化酶[超氧化物歧化酶 (SOD) 、过氧化氢酶 (CAT) ]活性和丙二醛 (MDA) 含量.结果 水迷宫实验中, 苦参素中、高剂量组大鼠逃避潜伏期、逃避路程均明显短于模型组 (P均＜0. 05) , 穿越平台次数均明显多于模型组 (P均＜0. 05) .跳台实验中, 苦参素中、高剂量组大鼠错误次数均明显少于模型组 (P均＜0. 05) , 受电击总时间均明显短于模型组 (P均＜0. 05) .苦参素中、高剂量组大鼠海马CA1区神经元形态结构变化和凋亡状况均明显轻于模型组, 神经元凋亡指数均显著低于模型组 (P均＜0. 05) , 海马中Bcl-2表达量及Bcl-2/Bax比值均明显高于模型组 (P均＜0. 05) , Bax表达量均明显低于模型组 (P均＜0. 05) .苦参素中、高剂量组大鼠海马组织中SOD、CAT活性均明显高于模型组 (P均＜0. 05) , MDA含量均明显低于模型组 (P均＜0. 05) .结论 苦参素具有改善慢性脑缺血大鼠学习记忆能力的作用, 其机制可能与调控海马组织凋亡相关基因表达而抑制海马神经元凋亡以及提高抗氧化酶活性而降低氧化应激损伤有关.
