A53T转基因小鼠体内α-突触核蛋白改变研究

Changes ofα-Synuclein in A53T Transgenic Mice

目的研究α-突触核蛋白(α-synuclein,α-syn)A53T转基因小鼠体内α-syn的分布和修饰变化情况。方法采用α-syn A53T转基因小鼠作为帕金森病(parkinson's disease,PD)模型小鼠,应用Western blot实验方法来检测A53T转基因小鼠和野生型C57BL/6小鼠的胃、黑质和纹状体中α-syn的表达含量和异常聚集情况。结果相比于野生型小鼠,A53T转基因小鼠的胃、黑质和纹状体中α-syn(C-20)、硝基化α-syn(n-syn)表达均显著增加;胃和黑质中的磷酸化α-syn(p-syn)含量降低,纹状体中p-syn含量升高;黑质和纹状体中寡聚体形式的α-syn(5G4)含量升高,胃中含量降低。其中,n-syn在胃组织中含量最高,寡聚体形式的α-syn在黑质部位含量最高,p-syn在纹状体部位含量最高。结论A53T转基因小鼠体内α-syn总蛋白增加,而异常修饰和聚集化的α-syn在不同器官内的含量变化有所差异,提示A53T相关的α-syn病变有组织特异性分布特点。

Objective To study the distribution and modification ofα-synuclein(α-syn)inα-synuclein A53T transgenic mice.Methods Theα-syn A53T transgenic mice were used as Parkinson's disease(PD)model mice.Western blot was used to detect the expression and abnormal aggregation ofα-syn in the stomach,substantia nigra and striatum of A53T transgenic mice and wild-type C57BL/6 mice.Results Compared with wild-type mice,the expressions of totalα-syn(C-20)and nitrosylatedα-syn(n-syn)in the stomach,substantia nigra and striatum of A53T transgenic mice increased.The content of phosphorylatedα-syn(p-syn)in the stomach and substantia nigra decreased,while the content of p-syn in the striatum increased.The content ofα-syn(5G4)in the form of oligomers in the substantia nigra and striatum increased,but decreased in the stomach.Among them,n-syn had the highest content in stomach tissues,α-syn in the form of oligomers had the highest content in the substantia nigra,and p-syn had the highest content in the striatum.Conclusion The totalα-syn protein in A53T transgenic mice increases,and the content of abnormally modified and aggregatedα-syn varies in different organs,suggesting that the pathological changes of the organs are specific in the pathogenesis of PD.