Wnt在胰岛素抵抗大鼠海马Aβ沉积中的作用及罗格列酮治疗前后Aβ的变化

Role of Wnt pathway in Aβ deposition in hippocampus of insulin resistant rats before and after treated with rosiglitazone

目的:探讨经典Wnt通路中的配体Wnt3a及下游胞内的β-catenin与胰岛素抵抗(IR)大鼠模型海马中β淀粉样肽(Aβ)沉积的关系;观察IR模型大鼠经罗格列酮治疗后,上述各指标的改变及与过氧化物酶体增殖物激活受体-γ(PPARγ)的相关性。方法:高糖、高脂、高蛋白饮食3个月造IR大鼠模型(IR),给予罗格列酮灌胃4周为治疗组(TZD);葡萄糖氧化酶法检测大鼠血糖水平,放免法检测血浆胰岛素水平,HOMA-IR评估胰岛素抵抗水平,蛋白印迹技术检测大鼠海马内Aβ、Wnt3a、β-catenin及PPARγ的水平。结果:IR组血浆胰岛素水平及胰岛素抵抗程度显著高于对照组。免疫印迹结果显示,IR组大鼠海马中Aβ及β-catenin表达增加,Wnt3a及PPARγ表达明显减少;经TZD干预后,大鼠海马中Aβ表达减少,Wnt3a、β-catenin及PPARγ表达增加。结论:胰岛素抵抗大鼠海马内Wnt信号通路水平下降可能是导致Aβ沉积的原因。罗格列酮作为PPARγ激动剂,可通过上调Wnt通路活性从而减少IR大鼠海马内Aβ的沉积。

AIM： To investigate the relationship between classical Wnt pathway with β- amyloid peptide（Aβ） deposition in hippocampus of insulin resistance（IR） rat model and to observe the above -mentioned proteins and the correlation with peroxisome proliferator- activated receptor γ（PPARγ） by treating the IR rats with rosiglitazone. METHODS： The rat models of IR and TZD were made. The plasma insulin and the plasma glucose levels were tested by RIA and glu- cose - oxidase methods, respectively. The indexes of insulin resistance were calculated by HOMA - 1R. The proteins of A13, Wnt3a, β-catenin and PPARγ were analyzed by Western blotting. RESULTS： The plasma insulin in IR group was significantly higher than that in control group. Insulin resistance, which was calculated by HOMA - IR, was significantly higher in IR group than that in control group. The levels of Aβ and β - catenin in IR group were higher than those in control group, while the levels of Wnt3a and PPAR-y were decreased. After treatment with rosiglitazone, Aβ was reduced but Wnt3a, β -catenin and PPARγ were increased. CONCLUSION： In hippocampus of 1R rats, Aβ is deposited and the lev- els of Wnt3a and Wnt are reduced. Rosiglitazone, as a PPARγ agonist, can upregulate the activity of Writ pathway and reduce Aβ deposition in rat hippocampus.