涤痰汤糖尿病大鼠认知功能障碍的保护作用及机制(1)
摘要 目的：观察涤痰汤对糖尿病大鼠认知能力的影响，并探讨其对PI3K-AKT信号通路相关因子的影响。方法：将30只SD鼠纳入研究，随机分为正常对照组、模型组及涤痰汤组，其中模型组及涤痰汤组大鼠均接受糖尿病模型制备，涤痰汤组用0.88 g/mL涤痰汤药液灌胃，正常对照组及模型组用等量的生理盐水灌胃，3组均连续灌胃28 d。各组采用水迷宫评估大鼠学习记忆功能，Tunel检测神经元细胞调亡情况，HE染色法观察海马组织病理结构改变，Western blotting法检测各组海马组织PI3K、AKT、p-AKT、Bax及Bcl-2蛋白水平变化。结果：涤痰汤可明显改善糖尿病模型大鼠的学习记忆能力，抑制神经元凋亡率及Bax水平，增加海马区PI3K、p-AKT、Bcl-2蛋白表达。结论：涤痰汤可明显改善糖尿病模型大鼠的认知，其作用机制可能与介导PI3K/AKT信号通路有关。
关键词 糖尿病模型;学习记忆能力;涤痰汤;水迷宫;海马;凋亡;PI3K-AKT信号通路;神经保护
Abstract Objective：To observe the effects of Ditan decoction on cognitive ability of diabetic rats and to explore the effects of Ditan decoction on PI3K-AKT signaling pathway related factors.Methods：A total of 30 SD rats were randomly divided into a normal control group，a model group and a Ditan decoction group.tTe rats in the model group and the Ditan decoction group were all prepared by the diabetic model，and the rats in the Ditan decoction group were treated with 0.88 g/mL Ditan decoction by gavage.The normal control group and the model group were given the same amount of normal saline intragastrically，and the 3 groups were continuously intragastrically administered for 28 days.The learning and memory function of rats in each group was evaluated by water maze，and the apoptosis of neurons was detected by tunnel.The pathological changes of hippocampus were observed by HE staining，and the levels of PI3K，AKT，p-AKT，Bax and Bcl-2 protein in hippocampus of each group were detected by Western blotting.Results：Ditan decoction could significantly improve the learning and memory ability of diabetic rats，inhibited the neuronal apoptosis rate and the level of Bax，and increased the expression of PI3K，p-AKT and Bcl-2 protein in hippocampus.Conclusion：Ditan decoction can significantly improve the cognition of diabetic rats，and its mechanism may be related to the mediation of PI3K/AKT signaling pathway.
Key Words Diabetic model; Learning and memory ability; Ditan decoction; Water maze; Hippocampal; Apoptosis; PI3K-AKT signaling pathway; Neuroprotection
中图分类号：R285.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2019.05.021
近年来越来越多的学者意识到研究糖尿病对认知的损伤具有重要临床意义，有文献[1-2]证实高血糖是导致认知障碍的独立危险因子，糖尿病患者罹患血管性痴呆的比例是普通人群的2.5倍，解剖学显示糖尿病脑病的病理变化与阿尔茨海默病(Alzheimersdisease，AD)即為相似，因此糖尿病患者是血管性痴呆的高危人群。
糖尿病脑损害引发的认知障碍属于中医学“健忘”“善忘”“呆病”等范畴，“百病多由痰作祟”“怪病多痰”，现代中医从“痰”入手治疗认知相关性疾病亦确有疗效。涤痰汤源自明代方贤著的《奇效良方》，具有涤痰开窍的功效，现代中医将其大量应用于认知及情志相关的疾病治疗[3-5]，获得了较为理想的疗效。但对其作用机制目前尚无统一定论，由此本团队以糖尿病模型为观察对象，探讨其相关机制，具体报道如下。
1 材料与方法
1.1 材料
1.1.1 动物 30只SPF(Speciifc Psthogen Free)级SD雄性大鼠纳入本研究，均购自长沙市天勤生物有限公司;许可证号为scxk(湘)2014-0010，scxk(湘)2014-0011。体质量180～220 g，平均体质量(201±1.92)g，鼠龄4～6个月，平均鼠龄(5±0.11)个月。所有大鼠均饲养于长春中医药大学实验中心SPF级实验动物房，室温控制在(22±1)℃，湿度(54±2)%，12 h/12 h交替光照。, 百拇医药(杨光磊 王国强 米佳)
关键词 糖尿病模型;学习记忆能力;涤痰汤;水迷宫;海马;凋亡;PI3K-AKT信号通路;神经保护
Abstract Objective：To observe the effects of Ditan decoction on cognitive ability of diabetic rats and to explore the effects of Ditan decoction on PI3K-AKT signaling pathway related factors.Methods：A total of 30 SD rats were randomly divided into a normal control group，a model group and a Ditan decoction group.tTe rats in the model group and the Ditan decoction group were all prepared by the diabetic model，and the rats in the Ditan decoction group were treated with 0.88 g/mL Ditan decoction by gavage.The normal control group and the model group were given the same amount of normal saline intragastrically，and the 3 groups were continuously intragastrically administered for 28 days.The learning and memory function of rats in each group was evaluated by water maze，and the apoptosis of neurons was detected by tunnel.The pathological changes of hippocampus were observed by HE staining，and the levels of PI3K，AKT，p-AKT，Bax and Bcl-2 protein in hippocampus of each group were detected by Western blotting.Results：Ditan decoction could significantly improve the learning and memory ability of diabetic rats，inhibited the neuronal apoptosis rate and the level of Bax，and increased the expression of PI3K，p-AKT and Bcl-2 protein in hippocampus.Conclusion：Ditan decoction can significantly improve the cognition of diabetic rats，and its mechanism may be related to the mediation of PI3K/AKT signaling pathway.
Key Words Diabetic model; Learning and memory ability; Ditan decoction; Water maze; Hippocampal; Apoptosis; PI3K-AKT signaling pathway; Neuroprotection
中图分类号：R285.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2019.05.021
近年来越来越多的学者意识到研究糖尿病对认知的损伤具有重要临床意义，有文献[1-2]证实高血糖是导致认知障碍的独立危险因子，糖尿病患者罹患血管性痴呆的比例是普通人群的2.5倍，解剖学显示糖尿病脑病的病理变化与阿尔茨海默病(Alzheimersdisease，AD)即為相似，因此糖尿病患者是血管性痴呆的高危人群。
糖尿病脑损害引发的认知障碍属于中医学“健忘”“善忘”“呆病”等范畴，“百病多由痰作祟”“怪病多痰”，现代中医从“痰”入手治疗认知相关性疾病亦确有疗效。涤痰汤源自明代方贤著的《奇效良方》，具有涤痰开窍的功效，现代中医将其大量应用于认知及情志相关的疾病治疗[3-5]，获得了较为理想的疗效。但对其作用机制目前尚无统一定论，由此本团队以糖尿病模型为观察对象，探讨其相关机制，具体报道如下。
1 材料与方法
1.1 材料
1.1.1 动物 30只SPF(Speciifc Psthogen Free)级SD雄性大鼠纳入本研究，均购自长沙市天勤生物有限公司;许可证号为scxk(湘)2014-0010，scxk(湘)2014-0011。体质量180～220 g，平均体质量(201±1.92)g，鼠龄4～6个月，平均鼠龄(5±0.11)个月。所有大鼠均饲养于长春中医药大学实验中心SPF级实验动物房，室温控制在(22±1)℃，湿度(54±2)%，12 h/12 h交替光照。, 百拇医药(杨光磊 王国强 米佳)