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Expression changes of nuclear factor-κB and nerve adhesion molecules in hippocampus of rats with delayed encephalopathy after acute carbon monoxide poisoning |
Gu Gang-feng, Peng Hong-yan, Lei Rui-qi, Jiang Li, Lv Xia, Wu Sha, Li Jing-lun |
Department of Neurology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China |
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Abstract Objective To discuss the mechanism of action of the dynamic expression of nuclear factor-κB (NF-κB), neural cell adhesion molecule (NCAM) and synaptic remodeling in delayed encephalopathy after acutel carbon monoxide poisoning (DEACMP), and to evaluate the intervention effect. Methods 120 male Sprague-Dawley (SD) rats were divided into air group (K group), carbon monoxide(CO) poisoning group (C group) and CO poisoning + PDTC group (P group), the rats were randomly divided into five subgroups according to the first day, the third day, the seventh day, the fourteenth day and the twenty-first day. Morris water maze, HE staining of hippocampus and electron microscopy were used to observe the changes of rat behaviour, cell and synaptic structure. The expression of NF-κB and NCAM in each group was detected by Western blot, immunofluorescence. Results In group C, cognitive dysfunction occurred after the fourteenth day, with necrosis and degeneration of hippocampal CA1 cells and sustained increase of NF-κB expression in hippocampus. The expression of NF-κB in group P decreased gradually after reaching its peak on the third day (IOD: 6940.84± 592.07), and the expression of NF-κB in group C was higher than that in group K and group P at each time point(P<0.05). The expression of NCAM in group C and P decreased gradually after the peak on the third day (IOD: 10 712.49 ±1091.66 vs. 18 020.52±1509.13), and the expression of NCAM in group P was more than that in group C and K at each time point,(P<0.05). The expression trend of Western blot was consistent with the results of immunofluorescence. Compared with groups K and P, the number of synapses and synaptic vesicles in hippocampal neurons in group C decreased with the damage of presynaptic membrane under electron microscope. Conclusion After CO poisoning, the neuronal cell death and hippocampal synaptic remodeling may be caused by up-regulating NF-κB expression. Pyrrolidinedithiocarbamate (PDTC) can inhibit NF-κB and promote NCAM expression, thus playing a role in protecting neurons.
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Corresponding Authors:
Li Jing-lun, E-mail: ljl031611@163.com
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[1]Guzman JA. Carbon monoxide poisoning[J]. Crit Care Clin, 2012, 28(4):537-548.
[2]Zhao N, Liang P, Zhuo X, et al. After treatment with methylene blue is effective against delayed encephalopathy after acute carbon monoxide poisoning[J]. Basic Clin Pharmacol Toxicol, 2018, 122(5):470-480.
[3]Gorman D, Drewry A, Huang YL, et al. The clinical toxicology of carbon monoxide[J]. Toxicology, 2003, 187(1):25-38.
[4]王佳, 杨俊卿, 余丽娟, 等. NF-κB抑制剂PDTC保护全脑缺血/再灌注大鼠海马损伤机制涉及COX2-PGI_2/TXA_2通路的初探[J].中国药理学通报,2014, 6:782-786.
[5]Snow WM, Stoesz BM, Kelly DM, et al. Roles for NF-κB and gene targets of NF-κB in synaptic plasticity, memory, and navigation[J]. Mol Neurobiol, 2014, 49(2):757-770.
[6]Westphal N, Theis T, Loers G, et al. Nuclear fragments of the neural cell adhesion molecule NCAM with or without polysialic acid differentially regulate gene expression[J]. Sci Rep, 2017, 7(1):13 631.
[7]Little EB, Crossin KL, Krushel LA, et al. A short segment within the cytoplasmic domain of the neural cell adhesion molecule (N-CAM) is essential for N-CAM-induced NF-kappa B activity in astrocytes[J]. Proc Natl Acad Sci USA, 2001, 98(5):2238-2243.
[8]Xiang W, Xue H, Wang B, et al. Efficacy of N-Butylphthalide and hyperbaric oxygen therapy on cognitive dysfunction in patients with delayed encephalopathy after acute carbon monoxide poisoning[J]. Med Sci Monit, 2017, 23:1501-1506.
[9]Goodrich-Hunsaker NJ, Hunsaker MR, Kesner RP . The interactions and dissociations of the dorsal hippocampus subregions: How the dentate gyrus, CA3, and CA1 process spatial information[J]. Behav Neurosci, 2008, 122(1):16-26.
[10]袁恒杰,陈宇华,任耘,等. 丹参素钠对大鼠脑缺血再灌注损伤耐缺氧作用研究[J]. 中国医院药学杂志,2010,30(18):1545-1549. |
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