Minocycline is effective in intracerebral hemorrhage by inhibition of apoptosis and autophagy
Minocycline is effective in intracerebral hemorrhage by inhibition of apoptosis and autophagy
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DOI：
10.1016/j.jns.2016.10.025
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发表时间：
2016-12-15
影响因子：
4.4
通讯作者：
Zhao, Fan
中科院分区：
文献类型：
--
作者：
Wu, Zehan;Zou, Xiang;Zhao, Fan
背景：脑出血是最难治疗的卒中类型，影响着全世界数百万人。ICH的治疗方法从药物到手术各不相同，但死亡率和流动性仍然很高。米诺环素是一种四环素类抗生素，因其神经保护潜力而日益受到认可。在早期的研究中，我们证明了在大鼠模型中注射米诺环素可以显著减少ICH引起的许多继发性损伤。以下研究探讨了米诺环素在减少脑损伤中的作用。方法：24只大鼠经右侧基底节注射100 μ l自体动脉血，用米诺环素或赋形剂治疗，并在第1、3和7天安乐死。结果：注射米诺环素后1、3、7 d，TUNEL阳性细胞明显减少，Beclin-1、LC 3BII/1、caspase-3/8表达均受到抑制。组织蛋白酶D和米诺环素之间的关系仍然未知。结论：我们的研究表明米诺环素的潜在药用价值，通过抗自噬和抗凋亡途径。(C)2016爱思唯尔B. V.保留所有权利。
Background: Intracerebral hemorrhage is the least treatable type of stroke and affects millions of people worldwide. Treatment for ICH varies from medicine to surgery, but the rate of mortality and mobility still remains high. Minocycline is a tetracycline antibiotic increasingly recognized for its neuroprotective potential. In earlier studies, we demonstrated that many secondary injuries caused by ICH could be significantly reduced by injection of minocycline in rat models. The following research investigates the role of minocycline in reducing brain injury.Methods: Twenty-four rats were administered 100 mu l autologous arterial blood injections into the right basal ganglia, treated with minocycline or vehicle and euthanized on the 1st, 3rd, and 7th day. lmmunohistochemistry, TUNEL, and western blot analysis were performed to analyze the effects of minocycline on apoptosis and autophagy.Results: After the injection of minocycline, TUNEL-positive cells were remarkably reduced on days 1, 3 and 7; Beclin-1, LC3BII/1, caspase-3/8 were all suppressed after treatment. The relationship between Cathepsin D and minocycline remained unknown.Conclusions: Our studies suggest the potential medicinal value of minocycline, through both anti-autophagy and anti-apoptosis pathways. (C) 2016 Elsevier B.V. All rights reserved.