2018 年第 6 期 第 13 卷

梓醇对高血糖阿尔茨海默病模型大鼠糖代谢的调节作用

Effect of catalpol on glycemic metabolism in hyperglycemic Alzheimer disease rat model

作者：张骐高峰刘倩刘倩倩孙秋爽杨娟珍王金红

英文作者：

单位：261053潍坊医学院药学院

英文单位：

关键词：阿尔茨海默病；梓醇；高血糖；糖代谢

英文关键词：

• 摘要：

• 【摘要】目的    观察梓醇对高血糖阿尔茨海默病（AD）模型大鼠糖代谢的调节作用。方法    50只Sprague Dawley（SD）大鼠采用完全随机方法并结合高血糖模型及处置方案分为正常对照组（10只）、高血糖组（10只）、高血糖AD模型组（9只）、梓醇组（9只）和吡格列酮组（6只）。β淀粉样蛋白片段25-35(Aβ25-35)注射前和注射后第7、14天进行Y迷宫实验，Aβ25-35注射前和注射后的第3、9、15天检测大鼠体质量、血糖、血清胰岛素。酶联免疫吸附试验方法检测大脑匀浆胰岛素及胰岛素样生长因子（IGF-1）含量，免疫组织化学方法观察其在大脑皮层的表达，蛋白质印迹法测其蛋白表达。结果    Aβ25-35注射后第7、14天，高血糖AD模型组大鼠的学习指数明显低于正常对照组，差异有统计学意义（P<0.01）；梓醇组和吡格列酮组大鼠的学习指数高于高血糖AD模型组，差异有统计学意义（P<0.01）。Aβ25-35注射后第9、15天梓醇组血糖明显低于高血糖AD模型组［（10.4±2.1）mmol/L比（17.4±0.9）mmol/L、（7.9±0.5）mmol/L比（19.2±0.8）mmol/L］，差异有统计学意义（P<0.05）。Aβ25-35注射后第15天，梓醇组和吡格列酮组血清胰岛素水平低于高血糖AD模型组［（14.8±1.7）、（15.1±1.7）mIU/L比（17.2±1.4）mIU/L］，差异有统计学意义（P<0.05）。高血糖AD模型组大脑匀浆胰岛素、IGF-1水平低于正常对照组；梓醇组和吡格列酮组大脑匀浆胰岛素、IGF-1水平高于高血糖AD模型组［（14.93±0.37）、（15.06±0.26）mIU/L比（13.70±0.54）mIU/L，（6.13±0.11）×105、（6.42±0.15）×105  ng/L比（3.44±0.19）×105  ng/L］，差异均有统计学意义（均P<0.05）。病理图片显示胰岛素和IGF-1阳性染色均分布在细胞质。与正常对照组比较，高血糖AD模型组大鼠阳性染色减少，梓醇组和吡格列酮组阳性染色比高血糖AD模型组颜色更深。电泳结果显示高血糖AD模型组的大脑胰岛素、IGF-1蛋白的表达水平明显低于正常对照组，梓醇组和吡格列酮组胰岛素、IGF-1蛋白的表达较高血糖AD模型组增加。结论    梓醇对高血糖AD大鼠的糖代谢过程有调节作用。

• 【Abstract】Objective    To observe the effect of catalpol on glycemic metabolism in hyperglycemic Alzheimer disease（AD） rat model. Methods    Fifty Sprague Dawley rats were randomly divided into normal control group(n＝10), hyperglycemia group(n＝10), hyperglycemic AD model group(n＝9), catalpol group(n＝9) and pioglitazone group(n＝6). Y-maze test was performed before injection and on the 7th, 14th day after injection of β-amyloid fragment 25-35(Aβ25-35). Body weight, blood glucose and serum insulin were detected before injection and on the 3rd, 9th, 15th day after injection of Aβ25-35. Contents of insulin and insulin-like growth factor(IGF-1) in brain homogenate were tested by enzyme-linked immunosorbent assay; expressions of insulin and IGF-1 were observed through immunohistochemical staining and western blotting. Results    Learning index in hyperglycemic AD model group was significantly lower than that in normal control group on the 7th, 14th day after injection of Aβ25-35（P<0.01）. Learning index in catalpol group and pioglitazone group was significantly higher than that in hyperglycemic AD model group（P<0.01）. Blood glucose level in catalpol group was significantly lower than that in hyperglycemia AD model group on the 9th, 15th day after injection of Aβ25-35［（10.4±2.1）mmol/L vs （17.4±0.9）mmol/L, （7.9±0.5）mmol/L vs （19.2±0.8）mmol/L］(P<0.05). Serum insulin level in catalpol group and pioglitazone group was significantly lower than that in hyperglycemic AD model group on the 15th day after injection of Aβ25-35［（14.8±1.7）,（15.1±1.7）mIU/L vs （17.2±1.4）mIU/L］(P<0.05). Levels of insulin and IGF-1 in brain homogenate in hyperglycemic AD model group were significantly lower than those in normal control group; levels of insulin and IGF-1 in brain homogenate in catalpol group and pioglitazone group were significantly higher than those in hyperglycemic AD model group［（14.93±0.37）,（15.06±0.26）mIU/L vs （13.70±0.54）mIU/L; （6.13±0.11）×105,（6.42±0.15）×105 ng/L vs （3.44±0.19）×105 ng/L］(P<0.05). Pathological images showed positive staining of insulin and IGF-1 in cytoplasm of cortical neurons; hyperglycemic AD model group showed cell cytoplasmic reduction and positive staining reduction compared with normal control group; insulin and IGF-1 positive staining increased in catalpol group and pioglitazone group. Electrophoretic results showed that expressions of insulin and IGF-1 in hyperglycemic AD model group were significantly lower than those in normal control group; expressions of insulin and IGF-1 in catalpol group and pioglitazone group were significantly higher than those in hyperglycemic AD model group. Conclusion    Catalpol regulates the glucose metabolism in hyperglycemic AD rats.