人参皂苷Rb_1和罗格列酮联合用药对2型糖尿病痴呆小鼠记忆功能的影响及机制

Effect and Mechanism of Ginsenosides Rb_1 and Rosiglitazone on Ethology and Insulin Signaling Pathway of Type 2 Diabetes Mice with Cognitive Impairment

目的:研究人参皂苷Rb1和罗格列酮联合用药对2型糖尿病记忆障碍小鼠动物学习记忆能力及胰岛素信号通路的影响。方法:雄性10周龄C57BL小鼠16只为正常组(N组),雄性10周龄Kkay小鼠64只为模型组,高糖高脂饲料喂养6周后,检测随机血糖≥13.9 mmol·L-1后随机分为模型组(M组)、阳性组(P组)、联合给药高、中、低剂量组(C1,C2,C3组)。P组每天用马来酸罗格列酮片按3.0 mg·kg-1灌胃,C组每天用马来酸罗格列酮片(3.0 mg·kg-1)和人参皂苷Rb1(60,30,15mg·kg-1)灌胃,N组和M组每天用等体积生理盐水灌胃,持续42 d。给药前后分别进行1次Morris水迷宫试验,记录结果并做比较。水迷宫后及时于冰上开颅取海马。采用酶联免疫吸附剂测定(ELISA)小鼠血浆胰岛素水平;半定量反转录-聚合酶链反应(RT-PCR)检测小鼠大脑海马中1-磷脂酰肌醇-3激酶亚基p85(PI-3K/p85)的信使核糖核酸(mRNA)表达水平。结果:与正常组相比,模型组在水迷宫试验中寻找平台的时间及错误率明显偏高(P<0.05),血浆胰岛素水平和PI-3K/p85水平均明显升高(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),血浆胰岛素水平和PI-3K/p85水平均明显降低(P<0.05)。结论:人参皂苷Rb1能在改善血浆胰岛素水平的基础上,有效提高胰岛素抵抗型糖尿病记忆障碍小鼠学习、记忆能力,其可能的作用机制为通过降低PI-3K/p85表达水平改善大脑海马胰岛素信号传导通路。

Objective：To study the effect and mechanism of ginsenosides Rb1 on memory impairment of type 2 diabetes.Method：Sixteen 10-week C57BL mice were as normal group （N group） and 64 Kkay mice 10-week with high blood sugar （≥13.9 mmol·L^-1） as model group （M group）,positive group （P group） and composite group with high,middle and low doses （C1,C2,C3 group）.Fed the positive group was given rosiglitazone maleate tablets （3.0 mg· kg^-1）,and composite group was given rosiglitazone maleate tablets （3.0 mg·kg-1） and ginsenosides Rb1 （60,30,15 mg·kg-1）.Normal and model groups were given equal volume of saline.After two Morris water mazes,samples were collected and enzyme-linked immunosorbant assay （ELISA） method wasused to test plasma insulin and reverse transcription polymerase chain reaction （RT-PCR） was used to test 1-phosphatidylinosital 3-kinase （PI-3 K）/p85.Result：Compared with normal group,model group used much longer time to find the plat （P 〈0.05）,had more active plasma insulin and PI-3K/p85 （P 〈0.05）.Compared with control group,there was no significant differences in positive group,while plasma insulin and PI3K/p85 were contrary in composite group （P 〈 0.05）.Conclusion：Ginsenosides Rb1 can improve the study and memory level of type 2 diabetes mice with cognitive impairment based on the reducing of plasma insulin,and the possible mechanism may reduce the level of PI-3K/p85.