《中国康复理论与实践》

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内皮素A受体拮抗剂BQ-123 对蛛网膜下腔出血大鼠学习记忆能力及海马区神经细胞自噬的影响①

刘俊杰1,赵旭2,赵雅宁1,李建民2,徐继伟1   

  1. 1.华北理工大学,河北唐山市063000;2.华北理工大学附属医院神经外科,河北唐山市063000。
  • 出版日期:2016-02-25 发布日期:2016-06-01

Effects of Endothelin A Receptor Antagonist BQ-123 on Learning and Memory Ability and Neurons Autophagy in Hippocampus in Rats with Subarachnoid Hemorrhage

LIU Jun-jie1, ZHAO Xu2, ZHAO Ya-ning1, LI Jian-min2, XU Ji-wei1   

  1. 1.North China University of Science and Technology, Tangshan, Hebei 063000, China; 2.Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei 063000, China
  • Published:2016-02-25 Online:2016-06-01

摘要: 目的探讨BQ-123 对蛛网膜下腔出血(SAH)大鼠学习记忆及海马区神经细胞自噬的影响。方法72 只成年雄性Sprague-Dawley 大鼠随机分为假手术组(n=24)、SAH模型组(SAH 组,n=24)和BQ-123 组(n=24)。二次注血法建立大鼠SAH模型,假手术组不注血,BQ-123 组于造模前30 min侧脑室注射BQ-123 18 μg。分别于术后6 h、24 h、72 h、144 h 应用穿梭箱测试大鼠遭受电击时被动回避潜伏期(PAL)、主动回避反应率(AARR);HE染色观察海马区神经细胞形态变化;免疫组化检测自噬相关因子Beclin-1 和LC3-Ⅱ的表达。结果与假手术组比较,SAH组各时间点PAL延长(P<0.05),AARR降低(P<0.05),海马区神经元数量减少(P<0.05),Beclin-1、LC-3Ⅱ蛋白阳性细胞增加;与SAH 组比较,BQ-123 组各时间点PAL 缩短(P<0.05),AARR 升高(P<0.05),海马区神经元数量增加(P<0.05),Beclin-1、LC-3-Ⅱ蛋白阳性细胞数增加。结论BQ-123 可促进SAH大鼠学习记忆功能恢复,其机制可能与激活海马区神经细胞自噬有关。

关键词: 蛛网膜下腔出血, BQ-123, 学习记忆, 自噬, 海马, 大鼠

Abstract: Objective To investigate the effect of BQ-123 on the ability of learning and memory and nerve cell autophagy in hippocampus in rats with subarachnoid hemorrhage (SAH). Methods 72 male Sprague-Dawley rats were randomly divided into sham group, SAH model group (SAH group) and BQ-123 group with 24 rats in each group. SAH model was established by injecting the autologous blood into cisterna magna twice. The sham group was not injected blood. BQ-123 group received intracerebroventricular injection with BQ-123 18 μg 30 minutes before modeling. 6, 24, 72 and 144 hours after modeling, the passive avoidance latency (PAL) and active avoidance reaction rate (AARR) were tested with Shutter Box Test, the nerve cell morphological changes of hippocampus were observed with HE staining, and the expressions of Beclin-1 and LC3-II were detected with immunohistochemical staining. Results Compared with the sham group, the PAL prolonged, the AARR decreased (P<0.05), the nerve cells in the hippocampus reduced (P<0.05), and the expressions of Beclin-1 and LC3-II increased (P<0.05) in SAH group. Compared with SAH group, PAL shortened (P<0.05), AARR increased (P<0.05), the nerve cells in the hippocampus increased (P<0.05), and the expressions of Beclin-1 and LC3-II increased (P<0.05) in BQ-123 group. Conclusion BQ-123 can promote the recovery of learning and memory ability, which may relate to the activation of nerve cell autophagy in the hippocampus.

Key words: subarachnoid hemorrhage, BQ-123, learning and memory, autophagy, hippocampus, rats