抑制NgR信号通路对糖尿病大鼠学习记忆的改善作用

目的:探讨Nogo受体(NgR)信号通路在糖尿病大鼠学习记忆中的作用及其可能机制。方法:雄性SD大鼠随机分为对照组、糖尿病组、siNgR组、siRNA空白组。除对照组外,其余各组均腹腔注射链脲佐菌素(60mg/kg)制备糖尿病模型。对照组、糖尿病组双侧海马CA1区注射病毒保存液10μl;siNgR组、siRNA空白组分别注射腺相关病毒包装的siNgR和病毒阴性对照液10μl。12周后水迷宫检测各组大鼠学习记忆能力。免疫荧光检测NgR、突触素(SYP)蛋白表达。免疫印迹检测海马NgR、SYP、生长相关蛋白43(GAP-43)蛋白表达。结果:与对照组相比,糖尿病组海马NgR、GAP-43表达均增多,SYP表达减少,学习记忆能力明显下降。与糖尿病组相比,siNgR组NgR表达减少,GAP-43、SYP表达均增多,学习记忆能力明显改善。siRNA空白组与糖尿病组相比无明显变化。结论:抑制NgR信号通路可改善糖尿病大鼠学习记忆能力,其机制可能与GAP-43、SYP蛋白表达上调有关。

Inhibiting NgR signaling pathway improves learning and memory in diabetic rats

Objective:To investigate the effect of NgR signaling pathway on learning and memory in diabetic rats and its possible mechanism.Methods:Sprague-Dawley rats were randomly divided into control group,diabetic group,siNgR group and siRNA group.The rats in each group(except for control group)were intraperitoneally injected with streptozotocin(60 mg/kg)to establish diabetic animal models.Rats in control group and diabetic group were injected with virus preservation solution(10μl)in the CA1 region of bilateral hippocampus while siNgR group and siRNA group were injected with AAV-packed siNgR and negative control solution(10μl).The Morris water maze was used for the evaluation of learning and memory.Immunofluorescent staining was performed to analyze protein expression of NgR and synaptophysin(SYP).Protein level of NgR,SYP and growth associated protein-43(GAP-43)was detected by Western blotting.Results:Compared with control group,diabetic group showed enhanced protein levels of NgR and GAP-43,decreased expression of SYP,and impaired learning and memory.Compared with diabetic group,siNgR group showed decreased expression of NgR,increased expression of GAP-43 and SYP,improved learning and memory.No significant protein expression was found between siRNA blank group and diabetic group.Conclusion:Inhibition of NgR signaling pathway improves the learning and memory of diabetic rats,which may be related to the up-regulation of GAP-43 and SYP expression.