山东医药2017，Vol.57Issue(11)：26-29,4.DOI:10.3969/j.issn.1002-266X.2017.11.008
腹腔注射雷帕霉素的实验性自身免疫性脑脊髓炎小鼠脊髓神经元病理变化及其机制
Pathological changes of spinal cord neurons in EAE mice with intraperitoneal injection of rapamycin
摘要
Abstract
Objective To investigate the pathological changes of spinal cord neurons in experimental autoimmune encephalomyelitis (EAE) mice with intraperitoneal injection of rapamycin and the mechanisms underlying it.Methods C57BL/6 mice were randomly divided into the control group, model group and observation group, 15 mice in each group.In the model group and observation group, we prepared the EAE models.The mice in the observation group were injected with rapamycin 0.75 mg/(kg·d) intraperitoneally and were injected with 0.5 mL of the pertussis bacteria dilution after 2 days and killed after 18 days.Collecting the spinal tissues to observe pathological changes with nissl staining, detecting the content of ROS with DCF chemical fluorescence, the expression of autophagy markers LC3-II/LC3-I and mTOR, Akt proteins in Akt/mTOR signaling pathway with Western blotting.Results Compared with the control group, the nissl bodies had smaller volumes, less number and fuzzy boundaries in spinal cord neurons of mice in the model group.Compared with the model group, the spinal cord neurons were neatly arranged, the number and the volume of the nissl bodies were increased, fuzzy boundaries phenomenons were rare in the observation group.The content of ROS in the control group, model group and observation group were (43.34±2.67), (84.22±3.15) and (64.10±3.59) U/mgprot, respectively.The content of ROS in the model group was higher than that of the control group (P<0.05).The content of ROS in the observation group was higher than that in the control group (P<0.05), which was lower than that in the model group (P<0.05).The autophagy marker LC3-Ⅱ/LC3-Ⅰstrip optical density (OD) values in the spinal cord tissues of three groups were 0.486±0.021, 0.251±0.032 and 0.566±0.054, respectively;the observation group was higher than the model group, and the model group was lower than the control group (all P<0.05).Meanwhile, the OD values of p-Akt and p-mTOR proteins in the model group were higher than those of the control group (both P<0.05), and the OD values of p-Akt and p-mTOR proteins in the observation group were lower than those of the control group and model group (all P<0.05).Conclusions Intraperitoneal injection of rapamycin reduces the pathological changes of spinal cord neurons in EAE mice.This may be due to the fact that rapamycin inhibits autophagic activity of AKT/mTOR/P70S6 pathway, removes ROS and inhibits oxidative stress.rapamycin can inhibit the mTOR signaling pathways to activate the autophagy activities, and reduce the ROS levels to inhibit the oxidative stress ,thus protecting the spinal cord neurons in EAE mice.关键词
雷帕霉素/实验性自身免疫性脑脊髓炎/细胞自噬/氧化应激/PI3K-AKT-mTOR通路Key words
rapamycin/experimental autoimmune encephalomyelitis/cell autophagy/oxidative stress/PI3K-AKT-mTOR signaling pathways分类
医药卫生引用本文复制引用
谢阳,黄远帅,杨元,李作孝..腹腔注射雷帕霉素的实验性自身免疫性脑脊髓炎小鼠脊髓神经元病理变化及其机制[J].山东医药,2017,57(11):26-29,4.基金项目
四川省卫生厅科研基金资助项目(120336). （120336）
