Zhang Yu-Lian, Zhou Zhen, Han Wen-Wen, Zhang Lin-Lin, Song Wan-Shan, Huang Jian-Hua, Liu Shuang
* Department of Neurology, Second Hospital Affiliated to Tianjin University of Traditional Chinese Medicine, Tianjin 300150, China.
† Institute of Traditional Chinese and Western Medicine, Huashan Hospital Fudan University, Shanghai 200040, China.
Am J Chin Med. 2016;44(1):103-17. doi: 10.1142/S0192415X16500075.
To investigate the effect of oleanolic acid (OA) on the differentiation of neural stem cells (NSCs) induced by A[Formula: see text] via regulating the JAK/STAT signaling pathway, a neurotoxicity cell model involving the induction of NSCs by soluble A[Formula: see text] (5 [Formula: see text]M) was used. The WST-1 method and immunofluorescence tests were used respectively to detect the activity of cell model and the expression of GFAP[Formula: see text]/DAPI and Tubulin[Formula: see text]/DAPI. Western blotting and real-time PCR analyses were used to observe the effects of OA on NSCs differentiation by examining key targets of the JAK/STAT signal transduction pathway. Compared with normal NSCs, A[Formula: see text]-induced NSCs had down-regulated expression of Ngn1 and up-regulated STAT3 expression and phosphorylation, and inhibited neuronal differentiation. OA treatment effectively inhibited the A[Formula: see text]-induced activation of JAK/STAT signaling, with a significant increase in Ngn1 expression and a significant decrease in p-STAT3/STAT3. These results indicate that OA could inhibit the excessive differentiation of NSCs into astrocytes by down-regulating JAK/STAT signaling which might retard the progress of AD.
为研究齐墩果酸(OA)通过调节JAK/STAT信号通路对Aβ诱导的神经干细胞(NSCs)分化的影响,使用了一种神经毒性细胞模型,该模型涉及用可溶性Aβ(5μM)诱导NSCs。分别采用WST-1法和免疫荧光试验检测细胞模型活性以及GFAP/DAPI和微管蛋白/DAPI的表达。采用蛋白质免疫印迹法和实时定量PCR分析,通过检测JAK/STAT信号转导通路的关键靶点,观察OA对NSCs分化的影响。与正常NSCs相比,Aβ诱导的NSCs中Ngn1表达下调,STAT3表达及磷酸化上调,神经元分化受到抑制。OA处理有效抑制了Aβ诱导的JAK/STAT信号激活,Ngn1表达显著增加,p-STAT3/STAT3显著降低。这些结果表明,OA可能通过下调JAK/STAT信号抑制NSCs过度分化为星形胶质细胞,这可能会延缓阿尔茨海默病(AD)的进展。