米诺环素对大鼠脑缺血再灌注损伤后学习记忆能力及海马神经元PSD-95蛋白表达的影响

Protective effects of low dose minocycline on spatial learning and memorizing ability and the expression of PSD-95 in rats after focal cerebral ischemia reperfusion

摘要:

目的：探讨静脉用低剂量米诺环素对局灶性脑缺血再灌注大鼠认知功能障碍及缺血侧海马生长相关蛋白-43（growth associated protein-43，GAP-43）和突触后致密物质-95（postsynaptic density 95，PSD-95）表达的影响。方法：采用线栓法建立Sprague-Dawley大鼠大脑中动脉阻塞再灌注模型，将45只雄性大鼠随机分为假手术组、模型组及米诺环素组（n=15）。分别采用免疫组织化学及免疫印迹法检测术后2周大鼠缺血侧海马GAP-43和PSD-95蛋白的表达，Morris水迷宫实验评价大鼠的行为学改变。结果：同假手术组相比，模型组大鼠缺血侧海马GAP-43（0.49±0.03）和PSD-95（0.92±0.04）表达明显增高（P=0.000）；大鼠逃避潜伏期明显延长[（44.2±10.0） s]，穿过原平台次数（2.6±0.9）和在目标象限探索时间百分率明显降低[（19.2±2.1）%，P=0.000）]。同模型组相比，尾静脉给予3 mg/kg米诺环素治疗后，大鼠缺血侧海马GAP-43（0.72±0.05）表达明显增加，PSD-95表达降低（0.67±0.05，P=0.000），大鼠逃避潜伏期明显缩短[（30.8±7.6） s，P=0.020]、穿过原平台次数（4.4±1.1，P=0.012）和在目标象限探索时间百分率明显增加[（30.4±2.7）%，P=0.000）]。结论：低剂量米诺环素能显著改善脑缺血再灌注后大鼠学习记忆能力，其机制可能与上调GAP-43和下调PSD-95表达有关。

Abstract:

Objective：To investigate the effects of low dose minocycline through vein on the spatial learning and memorizing ability and the expressions of growth associated protein-43（GAP-43） and postsynaptic density 95（PSD-95） in ischemic hippocampus of rats after focal cerebral ischemia/reperfusion（I/R）. Methods：The middle cerebral artery occlusion procedure was used to induce focal cerebral ischemia. Forty-five adult male Sprague-Dawley rats were randomly divided into sham-operated，I/R and minocycline groups. The GAP-43 and PSD-95 protein expression in ischemic hippocampus was measured by Western blot and immunohistochemistry，re－spectively. Morris water maze test was performed to detect the praxiology of rats after 2 weeks. Results：Compared with those in sham group，expression of GAP-43（0.49±0.03） and PSD-95（0.92±0.04） was significantly increased（P=0.000），escape latency was ex－tended（44.2±10.0） s，times of crossing the platform（2.6±0.9） and time percentage of swimming in target quadrant[（19.2±2.1）%，P=0.000] were significantly decreased in I/R group. Moreover，the rats in minocycline group demonstrated better spatial memory peformance than I/R group. The protein levels of GAP-43（0.72±0.05） was increased，PSD-95 was decreased（0.67±0.05，P=0.000），escape latency was shortened[（30.8±7.6） s，P=0.020]，times of crossing the platform（4.4±1.1，P=0.012） and time percentage of swimming in target quadrant[（30.4±2.7）%，P=0.000] were significantly decreased in minocycline group compared with those in I/R group（P=0.000）. Conclusion：Low dose intravenous minocycline improves the ability of learning and memorizing of rats after cerebral ischemia reperfusion，which may be partly associated with up-regulating GAP-43 and down-regulating PSD-95 pro－tein expression.