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中华神经创伤外科电子杂志

中华神经创伤外科电子杂志 ›› 2016, Vol. 02 ›› Issue (04) : 223 -227. doi: 10.3877/cma.j.issn.2095-9141.2016.04.008

所属专题： 文献；

基础研究

米诺环素改善血管性痴呆大鼠认知功能障碍的机制研究
庞慧1,†(), 刘怡1, 韩冰1, 付强1   
  1. 1. 221009　徐州，徐州市中心医院心内科
  • 收稿日期:2016-03-05 出版日期:2016-08-15
  • 通信作者: 庞慧

Minocycline prevents cognitive impairment in a rat model of vascular dementia

Hui Pang1,†(), Yi Liu1, Bing Han1, Qiang Fu1   

  1. 1. Department of Cardiovascular Medicine, XuZhou Central Hospital, Xuzhou 221009, China
  • Received:2016-03-05 Published:2016-08-15
  • Corresponding author: Hui Pang
  • About author:
    Corresponding author: Pang Hui, Email:
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庞慧, 刘怡, 韩冰, 付强. 米诺环素改善血管性痴呆大鼠认知功能障碍的机制研究[J]. 中华神经创伤外科电子杂志, 2016, 02(04): 223-227.

Hui Pang, Yi Liu, Bing Han, Qiang Fu. Minocycline prevents cognitive impairment in a rat model of vascular dementia[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2016, 02(04): 223-227.

目的

探索米诺环素是否在血管性痴呆导致的认知功能损害发生发展中发挥一定的神经保护作用，并进一步分析参与其中的相关分子机制。

方法

SD大鼠随机分为假手术组、模型组和米诺环素治疗组。结扎双侧颈总动脉建立大鼠血管性痴呆模型，术后腹腔注射米诺环素（25，50 mg/kg），28 d后进行水迷宫行为学实验检测认知变化，HE染色和Western blotting分析大鼠海马神经细胞凋亡的相关机制。

结果

（1）水迷宫认知功能测试显示，米诺环素能够显著缩短血管性痴呆大鼠寻找平台的潜伏期，并且明显延长在目标象限的停留时间，P<0.05为差异具有统计学意义。（2）HE染色显示米诺环素能够显著减轻模型组大鼠海马神经细胞损伤。（3）米诺环素治疗组含半胱氨酸的天冬氨酸蛋白水解酶-3（Caspase-3）蛋白表达水平及Bax/Bcl-2比值较模型组明显下降，P<0.05为差异具有统计学意义。（4）与模型组相比，米诺环素组磷脂酰肌醇3-激酶（PI3K）及磷酸化蛋白激酶B（p-AKT）蛋白表达水平明显升高，磷酸化糖原合酶激酶-3β（p-GSK-3β）蛋白表达却显著下降，P<0.05为差异具有统计学意义。

结论

米诺环素通过激活PI3K/AKT信号通路，抑制该通路下游靶分子GSK-3β活性，减少海马神经细胞凋亡的发生，在神经细胞保护和改善认知功能障碍中发挥重要作用。

关键词: 米诺环素, 血管性痴呆, 磷脂酰肌醇-3激酶, 蛋白激酶B, 糖原合酶激酶-3β
Objective

To explore the neuroprotective effect of minocycline on cognitive impairment in a rat model of vascular dementia (VD) and its potential molecular mechanism.

Methods

SD male rats were randomly divided into the sham-operation group, vascular dementia group and minocycline treated group. Rats were administered with minocycline by intraperitoneal injection after the surgery of bilateral common carotid artery occlusion. After 28 days, the Morris water maze test was carried out to test the spatial learning and memory ability of rats. The morphological changes of brain were observed by HE staining. Western blot was used to evaluate apoptosis mechanism of rat hippocampal neurons.

Results

(1)Minocycline treatment to VD rats significantly shortened the escape latency compared to the VD rats. In addition, Minocycline treated group spent more time in the target quadrant than the VD rats (P<0.05). (2)HE staining showed that minocycline could obviously protect the hippocampal neurons against damage in VD rats. (3)The protein expression of caspase-3 and Bax/Bcl-2 ratio in the minocycline administration group were significantly lower than those of the VD group (P<0.05). (4)Although minocycline decreased p-GSK-3β expression relatively to the VD group, the protein expression of PI3K and p-AKT in the minocycline treated group was significantly higher than that of the control group (P<0.05).

Conclusion

Minocycline protects against apoptosis of hippocampal neurons via the activation of PI3K/AKT signaling pathway and the inhibition of downstream target protein GSK-3β activity. Minocycline can play an important role in the protection of hippocampal neurons and the improvement of cognitive dysfunction.

Key words: Minocycline, Vascular Dementia, PI3K, AKT, GSK-3β
图1 米诺环素对血管性痴呆大鼠寻找平台潜伏期的影响
图2 米诺环素对血管性痴呆大鼠在目标象限停留时间的影响
图3 大鼠海马CA1区病理形态比较（HE染色，×400）
图4 Western blotting检测大鼠海马凋亡相关蛋白表达
图5 Western blotting检测大鼠海马PI3K-AKT-GSK-3β蛋白表达
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