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

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

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(60mg/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。

Objective To investigate the effect of aspirin（Asp）on cognitive function and the insulin-like growth factor-1receptor/phosphorylated insulin-like growth factor-1receptor（IGF-1R/p-IGF-1R）expression in the hippocampus of rats with diabetic encephalopathy,so as to analyze the protective mechanism of aspirin on brain.Methods Diabetes mellitus（DM）was induced by intraperitoneal injection of streptozotocin（STZ,60mg/kg body mass）.Rats were randomly assigned to four groups（n=10animals per group）,i.e.control,control＋ Asp,DM,and DM ＋ Asp groups.One week after the injection of STZ,the animals in Con＋Asp and DM＋Asp groups were gavaged with aspirin（10 mg/ [kg·d]）for 14 weeks.Meanwhile,the control group received the same dose of noromal saline for 14 weeks,and then the cognitive function was observed by Morris water maze（MWM）test in all rats.The expressions of IGF-1Rand p-IGF-1R proteins in the hippocampus of rats were examined by Western blotting analysis.Results The cognitive function of diabetic rats was improved after treated with aspirin：the escape latency of MWM test in DM ＋ Asp group was significantly shorter than that in DM group（P〈0.01）;the number of platform crossing and time spent in the target quadrant in the MWM test were significantly more in DM ＋ Asp group compared with those in DM group（P〈0.01 orP〈0.05）.H-E result showed that the neurons in DM ＋ Asp group were increased compared with that in DM group.The hippocampal expression of p-IGF-1Rprotein in DM group was significantly lower than that in the control group（P〈0.01）and aspirin treatment significantly increased p-IGF-1Rexpression（P〈0.01）.However,the IGF-1Rprotein levels in the hippocampus showed no significant difference between different groups.Conclusion Aspirin may protect the brain of rats with diabetic encephalopathy by regulating the IGF-1Rsignaling pathway.