药学学报, 2016, 51(6): 892-897
引用本文:
刘婷, 宋丹青, 张露勇, 胡培丽, 刘师卜, 左玮. 锌离子对大鼠局灶性脑缺血再灌注损伤模型中炎性反应的影响[J]. 药学学报, 2016, 51(6): 892-897.
LIU Ting, SONG Dan-qing, ZHANG Lu-yong, HU Pei-li, LIU Shi-bu, ZUO Wei. The effect of zinc on inflammatory reaction in rats with focal cerebral ischemia/reperfusion[J]. Acta Pharmaceutica Sinica, 2016, 51(6): 892-897.

锌离子对大鼠局灶性脑缺血再灌注损伤模型中炎性反应的影响
刘婷1,2,3, 宋丹青1, 张露勇2, 胡培丽2, 刘师卜2, 左玮3
1. 中国医学科学院、北京协和医学院医药生物技术研究所, 北京 100050;
2. 中国食品药品检定研究院, 北京 100050;
3. 中国医学科学院北京协和医院, 北京 100730
摘要:
观察锌离子螯合剂N-二硫氨基甲酸(DEDTC)对大鼠缺血性脑损伤的炎症反应的影响并对其作用机制进行研究。随机将200只雄性SD大鼠分为假手术组、局灶性脑缺血再灌注(I/R)组及DEDTC治疗组。采用线栓法建立大鼠大脑中动脉闭塞(MCAO)模型。分别于再灌注6、12和24 h时处死大鼠并取材。借助2,3,5-氯化三苯基四氮唑(TTC)法检测大鼠脑梗死体积;采用Newport Green (NG)染色法观察缺血半暗带区域锌离子的变化情况;以酶标记免疫吸附法(ELISA)测定脑组织中TNF-α和IL-6的浓度;最后通过Western blot的方法对PI3K/Akt/NF-κB信号通路的表达变化进行检测。结果显示, DEDTC显著减小大鼠的脑梗死体积,改善大鼠的神经功能,降低缺血再灌注损伤后脑组织中炎性因子的释放,抑制PI3K/Akt/NF-κB信号通路的激活。以上结果表明, DEDTC对大鼠局灶性脑缺血损伤具有一定的保护作用,其作用机制可能与抑制PI3K/Akt/NF-κB信号通路,降低炎性因子释放有关。
关键词:    锌离子      大脑中动脉闭塞模型      N-二硫氨基甲酸      炎性因子     
The effect of zinc on inflammatory reaction in rats with focal cerebral ischemia/reperfusion
LIU Ting1,2,3, SONG Dan-qing1, ZHANG Lu-yong2, HU Pei-li2, LIU Shi-bu2, ZUO Wei3
1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;
2. National Institutes for Food and Drug Control, Beijing 100050, China;
3. Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
Abstract:
This study was conducted to investigate the effect of N, N-diethyldithiocarbamate (DEDTC) on the changes of inflammatory cytokines after focal cerebral ischemia-reperfusion injury in rats and to explore the potential mechanism. Two hundred Sprague Dawley male rats were randomly divided into sham group, middle cerebral artery occlusion (MCAO) group and DEDTC (Zn chelator) treated group. MCAO model was established by the suture method. Rats were sacrificed at 6, 12 and 24 h after reperfusion. 2, 3, 5-Triphenyltetrazolium chloride (TTC) was conducted to measure the brain infarct volume. Newport Green was adopted to detect the chelatable zinc in the cerebral penumbra. Enzyme linked immunosorbent assay (ELISA) was performed to determine the release of TNF-α and IL-6. Furthermore Western blot was used to analyze the expression of the PI3K/Akt/NF-κB signaling pathway. The results showed that DEDTC resulted in a significant reduction of brain infarct volume and an obvious improvement of neurological function compared to the model group. DEDTC also decreased the release of inflammatory cytokines such as TNF-α and IL-6. The activation of PI3K/Akt/NF-κB signaling pathway induced by I/R injury was drastically inhibited by the treatment with DEDTC. In conclusion, DEDTC could protect the brain against ischemic injury induced by MCAO, which might be relevant to the inhibition of PI3K/Akt/NF-κB signaling pathway, and the decreased release of inflammatory cytokines.
Key words:    zinc    middle cerebral artery occlusion    N, N-diethyldithiocarbamate    inflammatory cytokine   
收稿日期: 2015-11-22
DOI: 10.16438/j.0513-4870.2015-1066
通讯作者: 左玮,Tel/Fax:86-10-69156513,E-mail:eileenzuo@163.com
Email: eileenzuo@163.com
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