碱性成纤维细胞生长因子对β-淀粉样蛋白诱导PC12细胞凋亡的抑制作用

目的:利用体外培养的PC12表现出神经细胞的特性,用Aβ_25-35诱导PC12细胞凋亡,建立神经细胞毒性作用的模型,来探索bFGF对Aβ_25-35作用和治疗老年性痴呆(AD)的机制。方法:通过Giema's、PI染色法、DNA琼脂糖凝胶电泳、Westernblot及流式细胞仪研究了加入Aβ_25-35培养的以及Aβ_25-35和bFGF共培养的PC12细胞的形态和分子生物学改变及凋亡相关基因Bcl-2,Bax表达的变化。结果:Aβ_25-35可诱导PC12细胞核DNA发生降解,出现染色质浓缩成块状、胞浆浓缩、胞膜内陷、凋亡小体形成等;而Aβ_25-35和bFGF共培养的PC12细胞则能缓解这种形态学上的变化,细胞凋亡率减少,Bcl-2的表达量上调而Bax的表达量下调。结论:bFGF能抑制Aβ_25-35对神经细胞的毒性作用,其机制可能是通过调控Bcl-2、Bax的表达来实现的。

Inhibitory effect of basic fibroblast growth factor on apoptosis induced by β-amyloid in PC12 cells

AIM:To clarify the effect of bFGF on the neurotoxity of Aβ_25-35 in PC12 cells and its potential application in the treatment of Alzheimer's disease. METHODS:Giema's, PI stainning, DNA agarose gel electrophoresis, Western blot and FCM were used to detect the morphological and biochemical changes of cultured PC12 cells treated with Aβ_25-35 and bFGF+ Aβ_25-35, and the expression of apoptosis-related gene bcl-2, bax. RESULTS:Morphological and biochemical characteristics of apoptosis, such as internuclear DNA fragmentation, compaction of nuclear chromatin, membrane blobbing, formation of apoptotic bodies, were observed in PC12 cells treated with Aβ_25-35. However, in PC12 cells treated with bFGF+ Aβ_25-35 , the above changes were significantly reversed, the expression of Bcl-2 was up-regulated while that of Bax was down-regulated. CONCLUSION:bFGF can inhibit the neurotoxity of Aβ_25-35 to neurons by regulating the expression of the apoptosis-related gene Bcl-2 and Bax.