人参皂苷Rb1与罗格列酮联合给药对2型糖尿病记忆障碍小鼠海马胰岛素信号传导通路的影响

Effect and Mechanism of Ginsenosides Rb1 on Insulin Signaling Pathway in Type 2 Diabetes Mice with Memory Impairment

摘要:

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。

Abstract:

Objective: To study the effect and mechanism of ginsenosides Rb₁ on memory impairment of type 2 diabetes. Method: C57BL mice were as normal control group and Kkay mice with high blood sugar as model l group. The model mice were divided into positive group and composite group with high, middle and low dose. The positive group was treated with Rosiglitazone maleate tablets(0.003 g·kg^-1)ig, and composite group was given the same Rosiglitazone tablets and ginsenosides Rb₁ (0.06, 0.03, 0.015 g·kg^-1) ig. After Morris water mazeimmunohistochemistry was used to assay 1-phosphatidy linosital 3-kinase(PI-3K)/Akt, and Western blotting was used to detect glycogen synthase kinase-3β GSK-3β, and p-Tau and insulin receptor(INSR) level. Result: INSR levels were almost the same in every group.Compared with normal control group, model group had more active PI-3K/Akt and lower GSK-3β and p-Tau level. Howere, compared with control group, there was no significant differences in positive group, while PI-3K/Akt was more active, and GSK-3β and p-Tau was contrary in composite group. Conclusion: Ginsenosides Rb₁ can improve the memory of type 2 diabetes mice, the possible mechanism may be related to improving insulin signaling pathway.