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  

Effects of Tripterine on Tau hyperphosphorylation induced by β-amyloid peptides in cultured SH-SY5Y cells

作　　者：曹帆帆[1] 徐莉敏[2] 王莹[1] 彭彬[1] 张雪[1] 张登海[1] 

机构地区：[1]第二军医大学附属公利医院中法合作中心实验室,上海200135 [2]第二军医大学附属公利医院检验科,上海200135

出　　处：《同济大学学报（医学版）》2016年第4期36-39,50,共5页Journal of Tongji University(Medical Science)

基　　金：上海市浦东新区卫生系统优秀青年医学人才培养计划(PWRq2013-11);上海市青年科技英才扬帆计划(15YF1410800)

摘　　要：目的观察雷公藤红素对β淀粉样蛋白1-42导致SH-SY5Y细胞Tau蛋白异常磷酸化的影响及其可能机制。方法用Aβ_(1-42)刺激SH-SY5Y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Aβ_(1-42)导致Tau蛋白异常磷酸化的变化,同时检测p-NF-κB表达情况;siRNA法下调TLR4表达,Western印迹法检测Aβ_(1-42)导致的Tau蛋白异常磷酸化的变化情况;同时观察下调TLR4后,Aβ_(1-42)刺激对p-NF-κB表达的影响。结果 Aβ_(1-42)刺激SH-SY5Y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;Aβ_(1-42)导致细胞p-NF-κB表达增加,雷公藤红素干预后p-NF-κB表达下调,且NF-κB抑制剂BAY11-7082同样能降低Aβ_(1-42)导致的Tau蛋白异常磷酸化;下调TLR4表达,Aβ_(1-42)导致的Tau蛋白异常磷酸化及p-NF-κB表达下降。结论雷公藤红素降低Aβ_(1-42)导致的SH-SY5Y细胞Tau蛋白异常磷酸化可能与其抑制TLR4/NF-κB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 Tan hyperphosphorylation and p-NF-nB induced by β-amyloid in SH-SY5Y cells were measured by Western blotting after TLR4 knocking down by siRNA. Results Compared with the control group, the expressions of Tan pSer199/202 and pSer396 were markedly increased after the induction of Aβ1-42, while the hyperphosphorylation of Tau pSer199/202 and pSer396 induced by Aβ1-42 was decreased by tripterine. The increasing of p-NF-kB expression induced by Aβ1-42 was decreased after the treatment of tripterine, and NF-r33 inhibitor BAY11-7082 also decreased the hyperphosphorylation of Tau pSer199/202 and pSer396 induced by Aβ1-42. The hyperphosphorylation of Tau pSer199/202 and pSer396 and p- NF-kB expression induced by Aβ1-42 was decreased after knocking-down TLR4. Conclusion Decreasing of Tau hyperphosphorylation by Tripterine is partially via inhibiting the TLR4/NF-kB signaling pathway.

关 键 词：雷公藤红素 β淀粉样蛋白 TAU蛋白 Toll样受体4 p-NF-κB 

分 类 号：R741[医药卫生—神经病学与精神病学]