Thy1-αSYN基因小鼠出现代谢紊乱和胰岛形态及功能的改变

帕金森病(PD) 是第二大神经退行性疾病。PD的发病机制仍然不明确，普遍认为 α-突触核蛋白(α-synuclein) 的聚集和传播引起的神经损伤、线粒体功能障碍、炎症和氧化应激，自噬功能障碍等在PD 的发生发展中发挥作用。越来越多的研究认为，代谢紊乱也是PD的发病机制之一。我们检测了过表达α-突触核蛋白是否能引起小鼠代谢紊乱以及可能的机制。研究分为Thy1-αSYN转基因小鼠组(TG)及同窝对照野生小鼠组（WT），分别检测它们在转棒仪上的停留时间，体重情况，血浆中胰岛素含量，小鼠糖耐量及胰岛素耐量等外周代谢情况。使用苏木精-伊红染色法对两组小鼠胰岛的形态进行观察，分离小鼠胰岛并使用葡萄糖刺激胰岛素分泌检测胰岛素分泌功能。结果显示, 12月龄的TG组小鼠与WT组相比运动耐力下降23.1%（P < 0.05），体重增加7%（P < 0.01），糖耐量降低（P < 0.05），胰岛素耐量降低（P < 0.05），外周血中胰岛素含量降低20%（P < 0.05）。TG组小鼠胰腺内α-突触核蛋白水平较WT组增加1.32倍（P < 0.05），TG组小鼠的胰岛面积变小（P < 0.05），胰岛个数减少（P < 0.01），胰岛素分泌功能下降（P < 0.01）。我们的研究提示，α-突触核蛋白在PD中的作用不局限于对多巴胺能神经元的损伤，它能影响代谢及外周器官的形态及功能，这为PD的发病机制提供新的理论依据。

Metabolic Disorder and Changes of Islets Morphology and Function in Thy1-αSYN Transgenic Mice

Parkinson’s disease (PD) is the second major neurodegenerative disease. The pathogenesis of PD is still unclear. It is generally believed that neural damage, mitochondrial dysfunction, inflammation, oxidative stress and autophagy dysfunction caused by the transmission and aggregation of α-synuclein play an important role in the occurrence and development of PD. More and more research show that metabolic disorder is one of the pathogenesis of PD. We examined whether overexpression of α-synuclein could induce metabolic disorder in mice and the possible mechanisms. Mice were divided into two groups: Thy1-αSYN transgenic mice (TG) and the control wild-type (WT) group. The rotarod test was used to analyze motor function in mice. We detected the body weight, plasma insulin content, glucose tolerance and insulin tolerance in the two group mice. The morphology of islets in the two groups were observed by hematoxylin eosin (HE) staining, and the islets were isolated to detect the glucose-stimulated insulin secretion (GSIS). The results showed that compared with the WT group, exercise tolerance of 12-month-old TG group decreased by 23.1% (P < 0.05), body weight increased by 7% (P< 0.01), glucose tolerance decreased (P < 0.05), insulin tolerance decreased (P < 0.05), and insulin contents in the peripheral blood decreased by 20% (P < 0.05). Compared with the WT group, the levels of α-syn proteins in the pancreas of the TG group increased by 1.32 times (P < 0.05), the area of islets in the TG group decreased (P < 0.05), the number of islets decreased (P < 0.01), and the insulin secretion function decreased (P< 0.01). This study showed that the role of α-synuclein in PD is not limited to the damage of dopaminergic neurons, it also can affect metabolism and the morphology and function of peripheral organs, which provides a new theoretical basis for the pathogenesis of PD.