Chloral Hydrate Preconditioning Protects Against Ischemic Stroke via Upregulating Annexin A1
Chloral Hydrate Preconditioning Protects Against Ischemic Stroke via Upregulating Annexin A1
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DOI：
10.1111/cns.12435
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发表时间：
2015-09-01
影响因子：
5.5
通讯作者：
Pei, Lei
中科院分区：
文献类型：
--
作者：
Liu, Jiu-Hong;Feng, Dan;Pei, Lei
目的预适应治疗缺血性脑卒中有希望。膜联蛋白A1（Annexin A1，ANXA 1）是一种体内平衡调节因子，参与对抗缺血性损伤。方法将成年雄性C57 BL/6 J小鼠或ANXA 1基因敲除（ANXA 1（-/-））小鼠随机分为对照组（NCH）和水合氯醛预处理（CH）组[2%、6%和10%水合氯醛（i. p.）大脑中动脉闭塞（MCAO）前1h]。神经功能评分采用改良7分量表和旋转棒试验。采用氯化三苯基四氮唑（TTC）染色和MRI分析脑梗死。ANXA 1，促炎细胞因子（TNF-，IL-1，IL-6）和炎症因子（IL-4，IL-10，TGF-β）的表达通过RT-PCR，Western blot和免疫荧光法进行了研究。此外，CH增加了小胶质细胞中ANXA 1的表达，降低了MCAO小鼠中TNF-α、IL-1和IL-6的水平，同时升高了IL-4、IL-10和TGF-β的水平。此外，ANXA 1阻断剂Boc 1（5 mg/kg，i. c. v.）结论水合氯醛预处理通过上调ANXA 1的表达，抑制CH对脑缺血的保护作用，其机制可能与增加ANXA 1的表达有关。
AimsPreconditioning is promising for treating cerebral ischemic stroke. Annexin A1 (ANXA1) is a homeostatic antiinflammatory mediator that participates in countering against ischemic injuries. We investigated whether chloral hydrate preconditioning (CH) exerts neuroprotection via regulation of ANXA1 in stroke.MethodsAdult male C57BL/6J mice or ANXA1 knockout (ANXA1(-/-)) mice were randomly allocated to control (NCH) and CH groups [2%, 6%, and 10% chloral hydrate (i.p.) 1h before the middle cerebral artery occlusion (MCAO)]. Neurological performances were evaluated by modified 7-point neurological scales and rotarod test. Cerebral infarction was analyzed by triphenyltetrazolium chloride (TTC) staining and MRI. The expression of ANXA1, pro-inflammatory (TNF-, IL-1, IL-6), and antiinflammatory (IL-4, IL-10, TGF-) cytokines was investigated by RT-PCR, western blot, and immunofluorescence.ResultsChloral hydrate preconditioning significantly improved the neurological outcomes and reduced the infarction and brain edema after ischemia. In addition, CH increased the expression of ANXA1 in the microglia, decreased the levels of TNF-, IL-1, and IL-6, while elevated the levels of IL-4, IL-10, and TGF- in the MCAO mice. Furthermore, both ANXA1 blocker Boc1 (5mg/kg, i.c.v.) or ANXA1 gene deficiency restrained the protective effects of CH against stroke.ConclusionsChloral hydrate preconditioning protects against ischemic injuries through upregulating the expression of ANXA1, and the followed antiinflammatory mechanisms.