雷公藤红素对β淀粉样蛋白诱导SH-SY5Y细胞Tau蛋白异常磷酸化影响的研究

观察雷公藤红素对β淀粉样蛋白142导致SHSY5Y细胞Tau蛋白异常磷酸化的影响及其可能机制。〖HT5”H〗方法〖HT5”K〗用 Aβ142刺激SHSY5Y细胞，建立Tau蛋白异常磷酸化的细胞模型。加入雷公藤红素干预，Western印迹法检测Aβ142导致Tau蛋白异常磷酸化的变化，同时检测pNFSymbolkA@B表达情况；siRNA法下调TLR4表达，Western印迹法检测Aβ142导致的Tau蛋白异常磷酸化的变化情况；同时观察下调TLR4后，Aβ142刺激对pNFSymbolkA@B表达的影响。〖HT5”H〗结果〖HT5”K〗Aβ142刺激SHSY5Y细胞，导致Tau蛋白Ser199/202、Ser396位点的磷酸化水平增加，而雷公藤红素能降低这两个位点磷酸化水平；Aβ142导致细胞pNFSymbolkA@B表达增加，雷公藤红素干预后pNF SymbolkA@B表达下调，且NFSymbolkA@B抑制剂BAY117082同样能降低Aβ142导致的Tau蛋白异常磷酸化；下调TLR4表达，Aβ142导致的Tau蛋白异常磷酸化及pNFSymbolkA@B表达下降。〖HT5”H〗结论〖HT5”K〗雷公藤红素降低Aβ142导致的SH SY5Y细胞Tau蛋白异常磷酸化可能与其抑制TLR4/NF SymbolkA@ B通路活性有关。
Objective To investigate the effects and mechanisms of tripterine on Tau hyperphospho rylation induced by β amyloid in SH SY5Y cells. Methods The effects of tripterine on the changes of Tau hyperphosphorylation and p NF SymbolkA@B induced by βamyloid in SHSY5Y cells were measured by Western blotting after TLR4 knocking down by siRNA. ResultsCompared with the control group, the expressions of Tau pSer199/202 and pSer396 were markedly increased after the induction of Aβ142, while the hyperphosphorylation of Tau pSer199/202 and pSer396 induced by Aβ142 was decreased by tripterine. The increasing of pNFSymbolkA@B expression induced by Aβ142was decreased after the treatment of tripterine, and NFSymbolkA@B inhibitor BAY117082 also decreased the hyperphosphorylation of Tau pSer199/202 and pSer396 induced by Aβ142. The hyperphosphorylation of Tau pSer199/202 and pSer396 and pNFSymbolkA@B expression induced by Aβ142 was decreased after knocking down TLR4. ConclusionDecreasing of Tau hyperphosphorylation by Tripterine is partially via inhibiting the TLR4/NFSymbolkA@B signaling pathway