阿司匹林对糖尿病脑病大鼠认知功能及海马IGF-1R/p-IGF-1R表达的影响

目的 观察阿司匹林对糖尿病脑病大鼠认知功能、海马组织胰岛素样生长因子1受体(IGF-1R)及磷酸化胰岛素样生长因子1受体(p-IGF-1R)表达的影响,探讨阿司匹林可能的大脑保护作用机制.方法 大鼠随机分为正常对照组(Con)、阿司匹林对照组(Con+Asp)、糖尿病脑病组(DM)和阿司匹林治疗组(DM+ Asp),每组10只,后2组大鼠采用一次性腹腔注射链脲佐菌素(60 mg/kg)建立糖尿病脑病大鼠模型,建模成功1周后,Con+ Asp组和DM+ Asp组给予阿司匹林10mg/(kg· d)]灌胃,Con组给以同等剂量生理盐水灌胃,持续14周.第14周时Morris水迷宫观察大鼠认知功能变化,蛋白质印迹法观察大鼠海马组织IGF-1R及p-IGF-1R表达的变化.结果 经阿司匹林治疗后,糖尿病大鼠认知功能得到改善:Morris水迷宫实验DM+Asp组逃避潜伏期短于DM组(P＜0.01);DM+ Asp组平台穿越次数、目的象限时间均多于DM组(P＜0.01或P＜0.05).H-E染色结果显示:DM+ Asp组海马神经元数量较DM组增多.与Con组相比,DM组海马区p-IGF-1R表达减少(P＜0.01),经阿司匹林治疗后糖尿病大鼠海马区p-IGF-1R表达增多(P＜0.01),但各组大鼠海马总IGF-1R蛋白水平差异无统计学意义.结论 阿司匹林可能通过调控IGF-1R信号通路对糖尿病脑病大鼠发挥脑保护作用.

Effect of aspirin on cognitive function and hippocampal IGF-1R/p-IGF-1R expression in rats with diabetic encephalopathy

Objective This study aimed to investigate the effect of aspirin on cognitive function and IGF-1R/p-IGF-1R expression in hippocampus of rats with diabetic encephalopathy and to analysis the protective mechanism of aspirin on brain. Methods Diabetes mellitus was induced by intraperitoneal injection of streptozotocin (60 mg/kg body weight). Rats were randomly assigned to four groups (n=10 animals per group), i.e. con, con Asp, DM, DM Asp. One week after the injection of STZ, gavage was performed with aspirin 10mg/ (kg?d)] for 14 weeks. 14 weeks later, cognitive function of all rats was observed in morris water maze (MWM) test. The expression of IGF-1R and p-IGF-1R levels was detected by western blot. Results After treated with aspirin, the cognitive function of diabetic rats was improved, the escape latency of MWM test was significantly shorter in DM Asp group than in DM group (P< 0.01), and the number of platform crossing and time spent in the target quadrant in probe trials of the MWM test were significantly more in DM Asp group than in DM group (P<0.01 or P<0.05). As shown in the HE result, the number of neuron increased in DM Asp group than in DM group. The expression level of p-IGF-1R protein was significantly lower in DM group than in control group (P<0.01) and the expression of p-IGF-1R was increased in hippocampus of diabetic rats after treated with Aspirin (P<0.01). However, the total IGF-1R protein level of hippocampus in each group showed no significant difference (P>0.05). Conclusion The decreased expression of p-IGF-1R in hippocampus may play an important role in the pathogenesis of diabetic encephalopathy. Aspirin may protect the brain of rats with diabetic encephalopathy by regulating the IGF-1R signaling pathway.