HDAC11对脑缺血/再灌注大鼠学习记忆的影响

Effects of HDAC11 on the learning and memory of rats after cerebral ischemia/reperfusion

目的 探讨组蛋白去乙酰化酶11（histone deacetylase 11，HDAC11）对脑缺血/再灌注（I/R）大鼠学习记忆能力的影响。方法 成年雄性SD大鼠随机分为假手术（Sham）组、模型（I/R）组、治疗（MGCD）组、聚乙二醇溶媒对照组（PEG组）。用四血管阻断法制作大鼠全脑I/R模型，Sham组大鼠仅给予双侧椎动脉阻断而不进行颈动脉结扎，MGCD组大鼠于造模前给予侧脑室注射MGCD0103（50 μg/kg）持续1周，PEG组用和给药组相同的给药方法给予PEG处理。于再灌注后的连续5天进行水迷宫实验来检测各组大鼠学习记忆能力的差异。结果 再灌注第2天至第5天，I/R组大鼠的潜伏期均长于Sham组（P〈0.05）；而MGCD组和I/R组相比，4天的逃避潜伏期均明显缩短（P〈0.05）。经过前4天的训练之后，撤去平台，大鼠在第4象限游泳的距离占所有象限的比例：I/R组低于Sham组（P〈0.05），MGCD组则高于I/R组（P〈0.05）。结论 运用HDAC11抑制剂可以减轻脑I/R对大鼠空间学习记忆能力的损伤， HDACll可能介导了脑I/R对空间学习记忆能力的损伤。

Objective To investigate the effects of histone deacetylase 11 （HDAC11） on the learning and memory of rats after cerebral ischemia/reperfusion （I/R）. Methods Adult male SD rats were randomly divided into four groups： a sham group, an modeling （I/R） group, a treatment （MGCD） group and a solvent control （PEG） group. A cerebral I/R model of rats was established by the four-vessel occlusion method. Rats in the sham group were occluded at the bilateral arteries without ligation of the carotid. The MGCD group was intracerebroventricularly injected with 50 μg/kg of MGCD0103 for 1 week before modeling. The PEG group was treated with PEG in the same way with the MBDC group. Morris water maze was performed for 5 days after reperfusion to observe the difference in learning and memory among the groups. Results From Days 2 to 5 after reperfusion, the I/R group showed longer latency than the Sham group （P〈0.05）. Meanwhile, compared with the I/R group, the MGCD group presented remarkably reduced escape latency （P〈0.05）. On Day 5 after reperfusion, rats were released into the pool without a platform. The percentages of the distance rats swam in the fourth quadrants divided by the distance rats swam in all quadrants were calculated, where the I/R group produced a lower percentage than the Sham group （P〈0.05）, but the MGCD group produced a higher percentage than the I/R group （P〈0.05）. Conclusions HDAC11 Inhibitor can relieve the damage of learning and memory in rats after cerebral I/R. HDAC11 may mediate the damage of learning and memory induced by cerebral I/R.