Han Bing, Wang Lijie, Fu Fenghua, Wang Zhenhua, Zhang Leiming, Qi Grace Jia, Wang Tian
Folia Neuropathol. 2018;56(2):133-140. doi: 10.5114/fn.2018.76618.
Autophagy is an intracellular degradation process that is involved in α-synuclein (α-syn) homeostasis and Parkinson's disease (PD). The purpose of this study was to investigate whether hydroxysafflor yellow A (HSYA) could promote α-syn clearance via regulating autophagy in PD mice. Male C57BL/6 mice were intraperitoneally treated with HSYA. Thirty minutes later, they were intragastrically administered with rotenone at a dose of 30 mg/kg. The hanging wire test was performed at 14 and 28 days. Then, autophagosomes and ultrastructural changes were examined by transmission electron microscopy. The expression of tyrosine hydroxylase (TH), α-syn, JNK1, p-JNK1, Bcl-2, p-Bcl-2, Beclin1, autophagy-related proteins (Atg) 7 and 12-5, and the LC3-II/LC3-I ratio were investigated by western blot. The hanging time of HSYA-treated PD mice was significantly increased compared with that of rotenone-induced PD mice (p < 0.05 or p < 0.01). Compared with rotenone-induced PD mice, treatment with HSYA augmented the formation of autophagosomes. The expression of TH, p-JNK1/JNK1, Beclin1, Atg7, Atg12-5, p-Bcl-2/Bcl-2, and the LC3-II/LC3-I ratio were significantly increased, whereas the expression of α-syn was reduced in the rotenone plus HSYA group. These results indicate that HSYA promoted α-syn clearance via regulating autophagy in rotenone-induced PD mice.
自噬是一种细胞内降解过程，参与α-突触核蛋白（α-syn）的稳态及帕金森病（PD）的发生。本研究旨在探讨羟基红花黄色素A（HSYA）是否可通过调节PD小鼠的自噬来促进α-syn的清除。雄性C57BL/6小鼠腹腔注射HSYA。30分钟后，以30 mg/kg的剂量给它们灌胃鱼藤酮。在第14天和第28天进行悬线试验。然后，通过透射电子显微镜检查自噬体和超微结构变化。通过蛋白质免疫印迹法检测酪氨酸羟化酶（TH）、α-syn、JNK1、p-JNK1、Bcl-2、p-Bcl-2、Beclin1、自噬相关蛋白（Atg）7和12-5以及LC3-II/LC3-I比率的表达。与鱼藤酮诱导的PD小鼠相比，HSYA治疗的PD小鼠的悬线时间显著延长（p < 0.05或p < 0.01）。与鱼藤酮诱导的PD小鼠相比，HSYA治疗增加了自噬体的形成。在鱼藤酮加HSYA组中，TH、p-JNK1/JNK1、Beclin1、Atg7、Atg12-5、p-Bcl-2/Bcl-2以及LC3-II/LC3-I比率的表达显著增加，而α-syn的表达降低。这些结果表明，HSYA通过调节鱼藤酮诱导的PD小鼠的自噬来促进α-syn的清除。
