关键词: 糖尿病, 脑病, 海马, β淀粉样肽42, 神经生长因子

Abstract:

Objective To observe the long-term changes in expression of amyloid β peptide(Aβ) 42 and nerve growth factor(NGF) in the hippocampus of experimental diabetic mice and to explore the mechanism of diabetic encephalopathy. Methods Sixty-four male mice were divided into a control(C) group(n=32) and a diabetic mellitus(DM) group(n=32) randomly. Streptozocin was freshly prepared and injected at 200 mg/kg, i.p. into mice which had been fasted for 12 h. Three days later, blood glucose in a tail-vein sample was determined; a value ≥15 mmol/L was accepted as a successful induction of a diabetic model. The expression changes of Aβ42 and NGF in the hippocampal CA1 region of C group and DM group mice were studied by immunohistochemical staining at the 4 time-points of 1 week, 4 weeks, 8 weeks and 12 weeks after DM models were established. Results 1. There were slightly stained Aβ42-positive cells in hippocampal CA1 region of C group mice, while more darkly stained Aβ42-positive cells in hippocampal CA1 region were found in DM group mice at the 4 time-points. The numbers of Aβ42-positive cells in hippocampal CA1 region of DM group mice at 1 week(14.10±3.60) increased a little compared with that of C group mice(13.20±3.08) with no significant difference(P>0.05), while the numbers of Aβ42-positive cells in the hippocampal CA1 region of DM group mice at 4 weeks, 8 weeks and 12 weeks(16.10±3.67, 16.20±2.86, 17.50±3.10) increased significantly(P<0.01) compared with those of C group mice(11.70±2.54, 12.00±2.67, 10.80±2.92). 2. That there were some darkly stained NGF-positive cells in hippocampal CA1 region of C group mice. DM group mice at the 4 time-points also had some NGF-positive cells in hippocampal CA1 region although the staining was a little pale. There were no significant differences between the numbers of NGF-positive cells in the hippocampal CA1 region of DM group mice at the 4 time-pointsand those of group C mice(P>0.05). Conclusion The expression of Aβ42 in the hippocampus of DM mice increased significantly compared with that of normal control mice at the middle stage of DM(4 weeks) and sustained till the end of this study(DM 12 weeks). The expression of NGF in the hippocampus of DM mice did not change significantly in this study. Aβ42 might be involved in the degenerative process of hippocampal neurons in DM mice and play an important role in the pathogenesis of diabetic encephalopathy.

Key words: diabetes mellitus, encephalophathy, hippocampus, amyloid &beta, peptide 42, nerve growth factor