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目的观察胰岛素抵抗(IR)大鼠脑组织β-淀粉样蛋白(Aβ)、淀粉样前体蛋白(APP)及其代谢相关酶的表达及吡格列酮(PIO)的干预效果。方法从45只Wistar大鼠中随机选取10只作为对照组(NC组),35只给予10%果糖水诱发胰岛素抵抗,4周后根据胰岛素抵抗指数(IRI),将制作成功的胰岛素抵抗模型26只大鼠随机分为IR组、PIO组。PIO组灌服吡格列酮(10 mg.kg-1.d-1)12周,IR组和NC组给予相同体积的生理盐水。免疫组化法观察大鼠海马Aβ42的表达;免疫印迹法检测大鼠脑APP、β-分泌酶(BACE1)、γ-分泌酶(PS1)的变化。结果IR组和PIO组大鼠海马Aβ42的表达明显高于NC组,与IR组相比,PIO组表达明显减低(P<0.01);与NC组相比,IR组和PIO组大鼠脑组织APP、BACE1及PS1的表达增高,PIO组表达较IR组减少(P<0.05)。结论胰岛素抵抗大鼠脑组织通过上调BACE1、PS1活性,使Aβ42生成增加;吡格列酮能抑制BACE1、PS1的表达,减少Aβ42生成。
Objective To observe the expression of β-amyloid protein (Aβ), amyloid precursor protein (APP) and their related enzymes in brain tissue of insulin resistance (IR) rats and the effect of pioglitazone (PIO) intervention. Methods Ten Wistar rats were randomly selected as the control group (NC group). 35 rats were given 10% fructose water to induce insulin resistance. After 4 weeks, the successful insulin resistance model was established according to the insulin resistance index (IRI) Only rats were randomly divided into IR group, PIO group. PIO group was given Pioglitazone (10 mg.kg-1.d-1) for 12 weeks, and the same volume of normal saline was given to IR and NC groups. The expression of Aβ42 in the hippocampus of rats was observed by immunohistochemistry. The changes of APP, β-secretase (BACE1) and γ-secretase (PS1) were detected by Western blotting. Results The expression of Aβ42 in hippocampus in IR group and PIO group was significantly higher than that in NC group (P <0.01). Compared with NC group, the expression of Aβ42 in IR group and PIO group was significantly higher than that in NC group The expression of APP, BACE1 and PS1 were increased, while PIO group was lower than IR group (P <0.05). Conclusion Pioglitazone could inhibit the expression of BACE1 and PS1 and decrease the production of Aβ42 by up-regulating the activity of BACE1 and PS1 in brain tissue of rats with insulin resistance.