β淀粉样肽前体蛋白N端肽段对糖尿病鼠脑凋亡相关改变的作用

目的　研究糖尿病小鼠海马内凋亡相关蛋白表达的变化及神经元是否凋亡。同时,观察β淀粉样肽前体蛋白N端 17肽(APP17肽)的作用。方法　用链脲佐菌素诱发小鼠糖尿病模型,并用APP17肽治疗。4wk后 ,行鼠脑冰冻切片,做Fas、Fas L、NF κB、早老素 1 (PS 1 )、α 共核蛋白 (α Syn)免疫组织化学染色,并检测神经元是否凋亡。结果　正常小鼠海马内有少量的Fas、Fas L、PS 1及α Syn阳性染色神经元,但糖尿病小鼠海马内Fas、Fas L、PS 1及α Syn阳性染色神经元数目比正常小鼠明显增加。正常小鼠海马表达NF κB的阳性神经元数目多,糖尿病小鼠海马内NF κB的阳性染色神经元数目比正常小鼠明显减少。用APP17肽保护后糖尿病小鼠上述各种蛋白质的表达恢复到接近正常小鼠的水平。在 3组小鼠海马切片中均未发现凋亡神经元。结论　糖尿病小鼠海马神经元发生了凋亡相关改变,但未发生明显凋亡现象。APP17肽可改善糖尿病小鼠海马内凋亡相关蛋白的表达,使神经元处于正常状态。

Apoptosis related changes in the brain of diabetic mice and the effect of amyloid precursor protein 17 mer peptide

Aim To investigate whether the changes of neuron ap op tosis related proteins exist in the brain of diabetic mice and to observe the ef fects of β-amyloid precursor protein (APP) 17-mer peptide on these changes. Methods Mouse diabetic model was produced with streptozotocin, and APP17-mer peptide was injected subcutaneously as a treatment. Four weeks la ter, brain slides of mice were studied by immunohistochemistry for Fas, Fas-L, NF-κB, Presenilin-1(PS-1), α-Synuclein and by TUNEL to observe the DNA f ragments of neurons.Results ① The number of neurons stained po sitively by Fas, Fas-L, PS-1, α-Syn antibodies in the brain of diabetic mice increased. In contrast to diabetic mice the number of positively stained hippocampal cells in normal mice were markedly reduced. The r esult of APP17 mer peptide-treated mice was the same as that in normal mice. Th e hippocampal neurons of diabetic mice showed significant intracellular decrease in NFκB. Treatment with APP 17mer peptide normalizes the expression of NFκB i n diabetic mice.② There were very little apoptotic neurons stained by TUNEL in the hippocampus of the three groups. Conc lusions The apoptosis related protein changes exist in the brain of dia betic mice. APP17mer peptide can normalize the expression of apoptosis related p roteins, indicating that APP17mer peptide can improve the apoptosis abnormalitie s of diabetic mice and retard neuronal degeneration.