吸烟对AD大鼠认知功能和tau蛋白异常磷酸化的影响

The effect and mechanism of cigarette smoking on cognitive function and abnormal phosphorylation of tau in AD rats

目的观察吸烟对AD大鼠认知功能和tau蛋白异常磷酸化的影响。方法AD大鼠吸烟12周，穿梭箱实验和Morris水迷宫检测学习记忆功能，免疫组化和免疫蛋白印迹技术检测tau（pS202）、tau（pT231）、tau-5和p38表达。结果吸烟组主动回避和被动回避次数[分别为（14．6±3．1）次，（24．6±3．3）次]少于不吸烟组[分别为（19．0±2．9）次，（32．6±3．8）次，P〈0．01]，吸烟组初次找到平台的时间[（18．32±4．70）s]多于不吸烟组[（14．38±6．28）s，P〈0．01]；吸烟组AD大鼠海马神经元CA1区tau（pS202）、p38阳性细胞数[分别为（31．1±4．44）个，（45．9±3．36）个]高于不吸烟组[（26．5±4．68）个，（25．9±3．96）个，P〈0．01]，与不吸烟组相比，吸烟组海马组织tau（pS202）、tau（pT231）磷酸化tau蛋白，tau-5蛋白和p38蛋白表达增加（P〈0．01）。结论AD大鼠吸烟后，认知功能损害加重，吸烟可能通过p38途径加强tau蛋白的异常磷酸化。

Objective To investigate the effect of cigarette smoking on cognitive function and abnormal phosphorylation of tau in AD rats. Methods The rats were injected Aβ25-35 at the 10th week during 12-weeks of cigarette smoking. Learning and memory function of AD rats were examined by shuttle box and Morris water maze. Immunohistochemical method and western blotting were used to analyze the expressions of tau （ pS202 ）, tau （ pT231 ）, tau-5 and p38. Results The times of AAR , PAR and spatial resolution of AD rats in smoking group decreased （ 14.6 ± 3.1,24.6 ± 3.3 vs 19.0 ± 2.9,32.6 ± 3.8 ） （ P 〈 0.01 ）. Compared with no smoking group, the time of finding fiat roof in smoking group is longer（ 18.32 ±4.70 vs 14.38 ±6.28） （ P〈0.01 ） . The expression of tau（pS202） and p38 positive ceils were significantly increased in CA1 of hippocampal neurons of smoking group （31.1 ± 4.44,45.9 ± 3.36 vs 26.5 ± 4.68,25.9 ± 3.96） （ P 〈 0.01 ）. The expression of tau （ pS202）, tau（pT231 ） and total tau protein as well as p38 were significantly increased in hippocampal neurons of smoking group （ P〈 0.01 ）. Conclusion Cigarette smoking can aggravate the cognitive impairment. Cigarette smoking can increase abnormal phosphorylation of tau by p38 pathway to facilitate the process of AD.