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目的:研究人参皂苷Rb1对2型糖尿病小鼠记忆功能及胰岛素信号传导通路的影响及作用机制。方法:C57BL小鼠为正常对照组,Kkay小鼠造模成功后根据血糖水平随机分为模型对照组、阳性组和复合给药高、中、低剂量组。阳性组用马来酸罗格列酮片(0.003 g·kg-1)ig,复合高、中、低剂量组分别用马来酸罗格列酮片(0.003 g·kg-1)ig和人参皂苷Rb1(0.06,0.03,0.015 g·kg-1)ig,其余用等体积生理盐水ig 6周。给药前、后各行1次Morris水迷宫实验;免疫组化方法检测大脑海马中1-磷脂酰肌醇-3激酶(PI-3K)水平;蛋白印迹法(Western blotting)检测糖原合酶激酶-3β(GSK-3β)、Tau蛋白及Tau蛋白磷酸化(p-Tau)和胰岛素受体(INS R)水平。结果:与正常组相比,模型组平台潜伏期明显升高(P<0.05),PI-3K活性明显偏低(P<0.05),GSK-3β和p-Tau水平均明显偏高(P<0.05);与模型组相比,罗格列酮组与之各项指标差异均不明显,复合给药组平台潜伏期均明显降低(P<0.05),PI-3K活性均明显升高(P<0.05),GSK-3β和p-Tau水平均明显降低(P<0.05);给药后各组间胰岛素受体水平差异无统计学意义。结论:在常规降糖的基础上,人参皂苷Rb1对2型糖尿病痴呆小鼠记忆水平有明显改善作用,其可能的作用机制为激活PI-3K蛋白、抑制GSK-3β表达、减轻Tau蛋白过度磷酸化,进而改善大脑海马胰岛素信号传导通路,阻止、延缓其相关神经病理进程。
Objective: To study the effect and mechanism of ginsenoside Rb1 on memory function and insulin signaling pathway in type 2 diabetic mice. Methods: C57BL mice were normal control group. Kkay mice were randomly divided into model control group, positive group and high, medium and low dose groups according to their blood glucose levels. Positive group with rosiglitazone maleate tablets (0.003 g · kg-1) ig, compound high, medium and low dose groups were treated with rosiglitazone maleate tablets (0.003 g · kg-1) ig and ginseng Saponin Rb1 (0.06,0.03,0.015 g · kg-1) ig, the rest with an equal volume of physiological saline ig for 6 weeks. Morris water maze test was performed on each line before and after administration. The level of 1-phosphatidylinositol 3-kinase (PI-3K) in the hippocampus was detected by immunohistochemistry. The levels of glycogen synthase kinase -3β (GSK-3β), Tau protein and Tau protein phosphorylation (p-Tau) and insulin receptor (INS R) levels. Results: Compared with the normal group, the latency of the model group was significantly increased (P <0.05), the activity of PI-3K was significantly lower (P <0.05) and the levels of GSK-3β and p-Tau were significantly higher ). Compared with the model group, there was no significant difference between the rosiglitazone group and the other indexes. The latency of the platform in the combination therapy group was significantly lower (P <0.05) and PI-3K activity was significantly increased (P <0.05 ), GSK-3β and p-Tau were significantly decreased (P <0.05). There was no significant difference in the level of insulin receptor between the two groups after administration. CONCLUSION: Ginsenoside Rb1 can significantly improve the memory of type 2 diabetic dementia mice on the basis of routine hypoglycemic mechanism. Its possible mechanism is to activate PI-3K protein, inhibit the expression of GSK-3β and reduce the excess of tau hyperphosphoric acid , And then improve the hippocampal insulin signal transduction pathway to prevent and delay its related neuropathological process.