Aβ25～35诱导大鼠记忆减退与星形胶质细胞及NOS阳性细胞变化

CHANGES OF NOS POSITIVE CELLS AND ASTROCYTES IN RATS WITH MEMORY DEFICIT INDUCED BY β-AMYLOID PEPTIDE FRAGMANT 25-35

目的 探讨Aβ2 5～ 3 5诱导模拟人类Alzheimer‘s病 (AD)的大鼠病理模型中星形胶质细胞变化与一氧化氮合酶神经元损伤引起的老年性记忆减退之间的关系。方法 双侧海马内注射 β-淀粉样多肽 2 5～ 3 5片段 (Aβ2 5～ 3 5 )制作大鼠AD模型 ,注射一周后采用NOS组化染色、GFAP免疫组化染色及NOS组化和GFAP双重染色分析大鼠海马GFAP与NOS的表达。结果 海马内注射Aβ2 5～ 3 5后出现海马星形胶质细胞增生、肥大、数目明显多于对照组 (P <0 0 5 ) ,并出现一氧化氮阳性星形胶质细胞 ;海马一氧化氮神经元数量较对照组显著减少 (P <0 0 5 )。结论 AD模型大鼠学习记忆功能低下与Aβ神经毒性导致NOS阳性神经元损伤、死亡直接相关 ,反应性星形胶质细胞参与Aβ导致NOS神经元细胞毒性损伤作用 。

Objective To study the relationship between astrocyte overexpression of glia fibrillary acidic protein(GFAP) and insults of NOS positive cells in rats with memory deficit induced by β-amyloid peptide fragment 25～35.Method Microinjection of Aβ 25～35 into the hippocampus induced the learning and memory dysfunction in rats. Nissl, NADPH-d histochemical and GFAP immunohistochemical staining were employed. Result Astroglia hypertrophy was seen in the rats injected with Aβ 25～35 in the hippocampus, and the number of GFAP positive cells increased markedly when compared with that of the controls (P<0.05). Forthemore, NOS positive astrocytes were detectable; and the number of NOS neurons in the hippocampus was much smaller in the model rats than in the controls (P<0.05).Conclusion The damage to NOS neurons by Aβ 25～35 may be directly correlated with the learning and memory deficit in the model rats with Alzheimer's disease, and the reactive astrocytes participate in this cytotoxicity procedure, indirectly causeing the learning and memory deficit.