[1]庞红利,宋俊杰,范军朝,等.七氟醚后处理对脑缺血再灌注损伤大鼠的保护作用及对Toll样受体4/核因子-κB信号通路的影响[J].新乡医学院学报,2020,37(1):021-25.[doi:10.7683/xxyxyxb.2020.01.006]
　PANG Hongli,SONG Junjie,FAN Junchao,et al.Protective effect of sevoflurane post-conditioning on cerebral ischemia-reperfusion injury rats and its effect on toll-like receptor 4/nuclear factor-κB signaling pathway[J].Journal of Xinxiang Medical University,2020,37(1):021-25.[doi:10.7683/xxyxyxb.2020.01.006]
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七氟醚后处理对脑缺血再灌注损伤大鼠的保护作用及对Toll样受体4/核因子-κB信号通路的影响
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
37
期数:
2020年1
页码:
021-25
栏目:
基础研究
出版日期:
2020-01-05

文章信息/Info

Title:
Protective effect of sevoflurane post-conditioning on cerebral ischemia-reperfusion injury rats and its effect on toll-like receptor 4/nuclear factor-κB signaling pathway
作者:
庞红利; 宋俊杰; 范军朝; 郑孝振
（河南大学第一附属医院麻醉科，河南　开封　475000）
Author(s):
PANG Hongli; SONG Junjie; FAN Junchao; ZHENG Xiaozhen
（Department of Anesthesiology,the First Affiliated Hospital of Henan University，Kaifeng 475000,Henan Province，China）
关键词:
七氟醚; 脑缺血再灌注损伤; Toll样受体4; 核因子-κB; 炎症; 氧化应激; 凋亡
Keywords:
sevoflurane; cerebral ischemia-reperfusion injury; Toll-like receptor 4; nuclear factor-κB; inflammation; oxidative stress; apoptosis
分类号:
R743；R971+.2
DOI:
10.7683/xxyxyxb.2020.01.006
文献标志码:
A
摘要:
目的　探讨七氟醚后处理对脑缺血再灌注损伤（CIRI）大鼠的保护作用及对Toll样受体4（TLR4）/核因子-κB（NF-κB）信号通路的影响。方法　将60只Sprague Dawley大鼠随机分为假手术组、CIRI组和七氟醚后处理组（Se组），每组20只。CIRI组和Se组大鼠采用线栓法制备CIRI损伤模型，假手术组大鼠不给予线栓。Se组大鼠于再灌注即刻给予体积分数2.5%七氟醚和氧气持续吸入30 min，氧流量1 L·min-1；假手术组和CIRI组大鼠持续吸入氧气30 min，氧流量1 L·min-1。再灌注24 h后采用改良神经功能缺损评分(mNSS)评估大鼠的神经功能，评估结束后取血并处死大鼠取出脑组织；检测各组大鼠脑梗死体积比、细胞凋亡指数、血清肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-6、IL-10和IL-1β水平、脑组织中丙二醛（MDA）水平及超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）的活性。Western blot法检测大鼠脑组织中Caspase-3、Bax、Bcl-2、TLR4及NF-κB p65蛋白的表达水平。结果　CIRI组和Se组大鼠mNSS评分、脑梗死体积比及细胞凋亡指数高于假手术组 （P＜0.05）；Se组大鼠mNSS评分、脑梗死体积比、细胞凋亡指数低于CIRI组 （P＜0.05）。与假手术组比较，CIRI组和Se组大鼠血清TNF-α、IL-6和IL-1β水平升高，IL-10水平降低（P<0.05）；与CIRI组比较，Se组大鼠血清TNF-α、IL-6和IL-1β水平降低，IL-10水平升高（P<0.05）。与假手术组比较，CIRI组和Se组大鼠脑组织中MDA水平及Caspase-3、Bax、TLR4、NF-κB p65蛋白表达水平显著升高，SOD、GSH-Px活性及Bcl-2蛋白表达水平显著降低（P<0.05）；与CIRI组比较，Se组大鼠脑组织中MDA水平及Caspase-3、Bax、TLR4、NF-κB p65蛋白表达水平显著降低，SOD、GSH-Px活性及Bcl-2蛋白表达水平显著升高（P<0.05)。 结论　七氟醚对CIRI大鼠脑组织具有一定的保护作用，其作用机制可能是通过抑制TLR4/NF-κB介导的炎性级联反应，减少炎性因子的释放，降低炎症和氧化应激反应，从而抑制细胞凋亡。
Abstract:
Objective　To investigate the protective effect of sevoflurane post-conditioning on cerebral ischemia-reperfusion injury (CIRI) rats，and its effect on toll-like receptor 4（TLR4）/nuclear factor-κB（NF-κB）signaling pathway.Methods　Sixty Sprague Dawley rats were randomly divided into sham group，CIRI group and sevoflurane post-conditioning group (Se group)，with 20 rats in each group.CIRI injury models of rats in the CIRI group and Se group were prepared by the method of wire bolting，rats in the sham group were not given bolting.The rats in the Se group was given volume fraction 2.5% sevoflurane and oxygen for 30 minutes in the beginning of reperfusion,oxygen flow rate was 1 L·min-1.And the rats in the sham group and the CIRI group were continuously given oxygen for 30 minutes，oxygen flow rate was 1 L·min-1.After 24 hours of reperfusion，modified neurologic severity score (mNSS) was used to evaluate the neural function of the rats.After scoring，blood was taken and the rats were sacrificed to remove the brain tissue.Cerebral infarction volume ratio，apoptotic index，serum levels of tumor necrosis factor-α (TNF-α)，interleukin(IL)-6，IL-10 and IL-1β and malondialdehyde (MDA) level，superoxide dismutase (SOD)，glutathione peroxidase (GSH-Px) activity in brain tissue were measured.The expression of Caspase-3，Bax，Bcl-2，TLR4 and NF-κB p65 protein were detected by Western blot.Results　The mNSS score，cerebral infarction volume and apoptotic index of the CIRI group and the Se group were significantly higher than those of sham group (P<0.05).The mNSS score，cerebral infarction volume and apoptotic index of the Se group were significantly lower than those of the CIRI group (P<0.05).Compared with the sham group，the serum levels of TNF-α，IL-6，IL-1β in the CIRI group and the Se group were significantly higher，while the level of IL-10 was significantly lower（P<0.05）.Compared with the CIRI group，the serum levels of TNF-α，IL-6，IL-1β in the Se group were significantly lower，while the level of IL-10 was significantly higher（P<0.05）.Compared with the sham group，the level of MDA and Caspase-3，Bax，TLR4，NF-κB p65 protein in the brain tissue of the CIRI group and the Se group were significantly higher，while SOD，GSH-Px activity and Bcl-2 protein expression level were significantly lower (P<0.05).Compared with the CIRI group，the levels of MDA and Caspase-3，Bax，TLR4，and NF-κB p65 protein in the Se group were significantly lower (P<0.05)，while the SOD，GSH-Px activity and Bcl-2 protein expression level were significantly higher (P<0.05).Conclusions　Sevoflurane has protective effect on brain tissue of CIRI rats.Its mechanism may be involve in inhibiting TLR4/NF-κB-mediated inflammatory cascade reaction，reducing the release of inflammatory factors，inflammation and oxidative stress response，and thereby inhibiting apoptosis.

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更新日期/Last Update: 2020-01-05