Pre-existing interleukin 10 in cerebral arteries attenuates subsequent brain injury caused by ischemia/reperfusion
Pre-existing interleukin 10 in cerebral arteries attenuates subsequent brain injury caused by ischemia/reperfusion
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脑动脉中预先存在的白细胞介素 10 可减轻随后由缺血/再灌注引起的脑损伤。
DOI：
10.1002/iub.1429
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发表时间：
2015-09-01
期刊：
影响因子：
4.6
通讯作者：
Chen, Si-Feng
中科院分区：
文献类型：
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作者：
Liang, Qiu-Juan;Jiang, Mei;Chen, Si-Feng
复发性中风很难治疗并且危及生命。抗炎基因的转移是缺血性中风的潜在基因治疗策略。使用重组腺相关病毒载体 1 (rAAV1) 介导的白细胞介素 10 (IL-10)，我们研究了在初次中风介入治疗期间将有益基因转移到大鼠脑血管中是否可以减轻复发性中风引起的脑损伤。将rAAV1-IL-10、rAAV1-YFP或盐水注入雄性Wistar大鼠的左大脑动脉中。基因转移三周后，大鼠左大脑中动脉（MCAO）闭塞45分钟，然后再灌注24小时。注射rAAV1-IL-10后3周，血清中IL-10水平显着升高，并且通过原位杂交证实脑血管中存在病毒。预先存在的IL-10（而非YFP）降低了神经功能障碍评分、脑梗塞体积和受损神经元细胞的数量。 AAV1-IL-10 转导增加了脑梗塞边界区血红素加氧酶 (HO-1) mRNA 和蛋白质水平。因此，缺血前脑动脉中IL-10基因的转导可减轻大鼠缺血/再灌注引起的脑损伤。这种预防复发性中风的方法可以在初次中风的介入治疗过程中实现。 (c) 2015 IUBMB 生活，67(9):710-719，2015
Recurrent stroke is difficult to treat and life threatening. Transfer of anti-inflammatory gene is a potential gene therapy strategy for ischemic stroke. Using recombinant adeno-associated viral vector 1 (rAAV1)-mediated interleukin 10 (IL-10), we investigated whether transfer of beneficial gene into the rat cerebral vessels during interventional treatment for initial stroke could attenuate brain injury caused by recurrent stroke. Male Wistar rats were administered rAAV1-IL-10, rAAV1-YFP, or saline into the left cerebral artery. Three weeks after gene transfer, rats were subjected to occlusion of the left middle cerebral artery (MCAO) for 45 min followed by reperfusion for 24 h. IL-10 levels in serum were significantly elevated 3 weeks after rAAV1-IL-10 injection, and virus in the cerebral vessels was confirmed by in situ hybridization. Pre-existing IL-10 but not YFP decreased the neurological dysfunction scores, brain infarction volume, and the number of injured neuronal cells. AAV1-IL-10 transduction increased heme oxygenase (HO-1) mRNA and protein levels in the infarct boundary zone of the brain. Thus, transduction of the IL-10 gene in the cerebral artery prior to ischemia attenuates brain injury caused by ischemia/reperfusion in rats. This preventive approach for recurrent stroke can be achieved during interventional treatment for initial stroke. (c) 2015 IUBMB Life, 67(9):710-719, 2015