Zhou Shouhong, Chen Xiong, Xue Ruirui, Zhou Qiaofeng, Hu Pengju, Ouyang Xinping, Dai Tingting, Zhu Wenting, Tian Shaowen
aDepartment of Physiology, Institute of Neuroscience, School of Medicine, University of South China, Hengyang bDepartment of Gastroenterology, the Third Xiangya Hospital, Central South University, Changsha cDepartment of Pediatrics, the First Affiliated Hospital, University of South China, Hengyang, China.
Neuroreport. 2016 Mar 23;27(5):337-44. doi: 10.1097/WNR.0000000000000543.
Recent studies have shown that autophagy is involved in peripheral nervous system disease. However, the role of autophagy in the pathogenesis of experimental autoimmune neuritis (EAN) remains unclear. Therefore, EAN was induced by a subcutaneous injection into both hind footpads of synthetic neuritogenic P2(57-81) peptide in male Lewis rats. The clinical evaluation was completed using a 10-point scale method. The histological alteration of sciatic nerves was analyzed by hematoxylin and eosin and luxol fast blue staining. The ultrastructure of sciatic nerves was analyzed by transmission electron microscopy. Expressions of beclin-1 and microtubule-associated protein light chain-3 (LC3) and p62/SQSTM1 were determined by western blot. 3-Methyladenine, the inhibitor of autophagy, was used in this research. Results showed that the clinical scores were significantly increased from day 6 to day 16 after immunization compared with the control group. Compared with the control group, the number of inflammatory cells and the histological score of sciatic nerves were significantly increased, expressions of beclin-1 and LC3-II and the ratio of LC3-II/LC3-I in the sciatic nerve were significantly increased, and the expression of p62 was significantly decreased in the EAN model group. Considerable double-membrane autophagosomes in axons and myelin sheaths of sciatic nerves were observed and the number of autophagosomes in axons and myelin sheaths of sciatic nerves in the EAN model group was obviously increased compared with the control group. 3-Methyladenine ameliorated the neurologic severity of EAN. Our results suggest that autophagy activity in nerve tissue of EAN rats is increased, which may be associated with the pathogenesis of EAN.
最近的研究表明，自噬参与外周神经系统疾病。然而，自噬在实验性自身免疫性神经炎（EAN）发病机制中的作用仍不清楚。因此，通过向雄性Lewis大鼠的双侧后足垫皮下注射合成的致神经炎P2（57 - 81）肽来诱导EAN。使用10分制方法完成临床评估。通过苏木精和伊红染色以及Luxol固蓝染色分析坐骨神经的组织学改变。通过透射电子显微镜分析坐骨神经的超微结构。通过蛋白质免疫印迹法测定beclin-1、微管相关蛋白轻链3（LC3）和p62/SQSTM1的表达。本研究使用了自噬抑制剂3-甲基腺嘌呤。结果显示，与对照组相比，免疫后第6天至第16天临床评分显著增加。与对照组相比，EAN模型组坐骨神经的炎性细胞数量和组织学评分显著增加，坐骨神经中beclin-1和LC3-II的表达以及LC3-II/LC3-I的比值显著增加，p62的表达显著降低。在坐骨神经的轴突和髓鞘中观察到大量双膜自噬体，与对照组相比，EAN模型组坐骨神经轴突和髓鞘中的自噬体数量明显增加。3-甲基腺嘌呤改善了EAN的神经严重程度。我们的结果表明，EAN大鼠神经组织中的自噬活性增加，这可能与EAN的发病机制有关。
