α7 nicotinic acetylcholine receptor agonist inhibits the damage of rat hippocampal neurons by TLR4/Myd88/NF‑κB signaling pathway during cardiopulmonary bypass.
α7 nicotinic acetylcholine receptor agonist inhibits the damage of rat hippocampal neurons by TLR4/Myd88/NF‑κB signaling pathway during cardiopulmonary bypass.
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DOI：
10.3892/mmr.2017.7166
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发表时间：
2017-10
影响因子：
3.4
通讯作者：
Zhang T
中科院分区：
文献类型：
--
作者：
Chen K;Sun Y;Diao Y;Ji L;Song D;Zhang T
本研究旨在探讨α7烟碱乙酰胆碱受体(α7nAChR)激动剂对体外循环(CPB)海马神经元损伤及Toll样受体4(TLR4)/髓样分化初级反应88(Myd88)/核因子(NF)-κB信号通路相关因子表达的影响。 Sprague Dawley大鼠随机分为五组：假手术组（Sham）；体外循环； CPB + α7nAChR 激动剂 PHA568487 (PHA)； CPB + α7nAChR 抑制剂 MLA (MLA)；和 CPB + PHA568487 + TLR4 拮抗剂 (CPT)。停止 CPB 后 12 小时采集血液和脑组织样本。使用ELISA测量血清炎症因子[白细胞介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α]和脑损伤标志物[S-100β和神经元特异性烯醇化酶(NSE)]的水平。此外，使用苏木精和伊红染色以及隧道实验观察病理组织学和细胞凋亡的变化。采用定量聚合酶链反应和蛋白质印迹法测定海马中TLR4、Myd88和NF-κB mRNA和蛋白的表达。 Sham组海马锥体细胞形态正常。 CPB、MLA、CPT组锥体细胞排列疏松，基线消失，细胞核固缩明显，神经元凋亡。此外，PHA组的细胞受到轻微损伤。 CPB、MLA、CPT组IL-1β、IL-6、TNF-α、S-100β、NSE表达水平均显着高于Sham组（P<0.05）。与CPB组比较，PHA组炎性细胞因子表达量显着降低（P<0.05）。 CPB、MLA、CPT组海马TLR4、Myd88、NF-κB mRNA及蛋白表达量显着高于Sham组，PHA组表达量显着低于CPB组（P<0.05）。 α7nAChRs激动剂可以抑制CPB诱导的大鼠脑神经元凋亡，并可能通过TLR4/Myd88/NF-κB信号通路保护脑损伤。
The present study aimed to investigate the effect of α7 nicotinic acetylcholine receptor (α7nAChR) agonist on the damage of hippocampal neurons and the expression of toll like receptor 4 (TLR4)/myeloid differentiation primary response 88 (Myd88)/nuclear factor (NF)-κB signal pathway-associated factors in cardiopulmonary bypass (CPB). Sprague Dawley rats were randomly divided into five groups: Sham operation (Sham); CPB; CPB + α7nAChR agonist PHA568487 (PHA); CPB + α7nAChR inhibitor MLA (MLA); and CPB + PHA568487 + TLR4 antagonist (CPT). Blood and brain tissue samples were harvested at 12 h following the withdrawal of CPB. Levels of serum inflammatory factors [interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α] and brain injury markers [S-100β and neuron-specific enolase (NSE)] were measured using ELISA. In addition, pathological histology and apoptosis changes were observed using hematoxylin and eosin staining, and Tunnel assays. Quantitative polymerase chain reaction and western blot assays were used to determine the expression of TLR4, Myd88 and NF-κB mRNA, and protein in the hippocampus. The morphology of hippocampal pyramidal cells in the Sham group was observed to be normal. Pyramidal cells in the CPB, MLA and CPT groups were loosely arranged, and the baselines had disappeared, with clear nucleus pyknosis and neuronal apoptosis. Furthermore, the cells in the PHA group were slightly damaged. IL-1β, IL-6, TNF-α, S-100β and NSE expression levels in the CPB, MLA, and CPT groups were significantly higher compared with that in the Sham group (P<0.05). Compared with CPB group, the expression of inflammatory cytokines in the PHA group was significantly lower (P<0.05). The expression of TLR4, Myd88 and NF-κB mRNA, and protein in the hippocampus of CPB, MLA and CPT groups were significantly higher compared with that in the Sham group, and the PHA group expression was significantly lower compared with the CPB group (P<0.05). α7nAChRs agonist can inhibit the apoptosis of rat brain neurons induced by CPB, and may protect against brain injury through the TLR4/Myd88/NF-κB signaling pathway.
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影响因子：
16.6
作者：
Carnevale, Daniela;Perrotta, Marialuisa;Pallante, Fabio;Fardella, Valentina;Iacobucci, Roberta;Fardella, Stefania;Carnevale, Lorenzo;Carnevale, Raimondo;De Lucia, Massimiliano;Cifelli, Giuseppe;Lembo, Giuseppe
通讯作者：
Lembo, Giuseppe
影响因子：
9.3
作者：
Zhu HT;Bian C;Yuan JC;Chu WH;Xiang X;Chen F;Wang CS;Feng H;Lin JK
通讯作者：
Lin JK
影响因子：
3.8
作者：
Arevalo-Serrano, J.;Sanz-Anquela, J. M.;Gonzalo-Ruiz, A.
通讯作者：
Gonzalo-Ruiz, A.
影响因子：
2.1
作者：
Cao, Hui-juan;Sun, Ying-jie;Diao, Yu-gang
通讯作者：
Diao, Yu-gang
影响因子：
1.6
作者：
Boehne, Martin;Sasse, Michael;Jack, Thomas
通讯作者：
Jack, Thomas