【摘 要】
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Tobacco smoking, a widely spread habit, has been found associated with declined cognitive functions.Fasudil, an inhibitor of Rho-associated coiled-coil kinase, possesses a strong neuroprotective poten
【机 构】
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School of Pharmaceutical Sciences, South-Central University for Nationalities,Wuhan 430074, PR China
【出 处】
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中国民族医药学会药品临床评价分会2016年学术年会
论文部分内容阅读
Tobacco smoking, a widely spread habit, has been found associated with declined cognitive functions.Fasudil, an inhibitor of Rho-associated coiled-coil kinase, possesses a strong neuroprotective potential.The current study was designed to investigate the pathological changes in brain and lung induced by smoke exposure, and explore whether fasudil could alleviate these impairments.Adult C57BL/6 mice were exposed to tobacco smoking for four months, and fasudil was treated from the third months.To investigate lung injuries, the immunohistochemistry of lung tissue, immune cell infiltrations, cytokine productions in bronchoalveolar lavage (BAL) fluid, and seurm inflammatory cytokines were evaluated.To investigate cognitive impairments, Morris water maze test, hippocampal inflammatory cytokines and associated signaling pathways were evaluated.Out finding showed fasudil administration inhibited the inflitration of inflammatory cells (macrophages, neutrophils, and lymphocytes), suppressed the production of inflammatory cytokines both in the BAL fluid and serum.Further, fasudil treatment significantly improved the spatial learning and memory impairments as indicted in Morris water maze test and reduced the elevation of hippocampal inflammatory cytokines induced by tobacco smoking.Of note,expressions of RhoA, ROCK1, ROCK2, caspase-3, caspase-9, bax and the phosphorylation of NF-kBp65, IkBα, IKKα and IKKβ were increased accompanying the smoke exposure-induced cognitive impairments, which were significantly restored by fasudil treatment as indicted in western blot and immunohistochemistry analysis.Together, our results showed that fasudil exhibited protective effects on smoke exposure induced cognitive deficits which might involve with the regulation of Rho/ROCK/NF-kB pathways.
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