• 首页
  • 期刊介绍
  • 编委会
  • 投稿指南
  • 期刊订阅
  • 广告合作
  • 留言板
  • 联系我们
  • English
张沁丽,王玉芬,刘 红,刘博雯.阿托伐他汀对自身免疫性脑脊髓炎小鼠髓鞘修复及 RhoA/ Rock1 通路的影响[J].中国比较医学杂志,2022,32(4):68~76.
阿托伐他汀对自身免疫性脑脊髓炎小鼠髓鞘修复及 RhoA/ Rock1 通路的影响
Effects of atorvastatin on myelin repair and the RhoA / Rock1 pathway in mice with autoimmune encephalomyelitis
投稿时间:2021-03-02  
DOI:10. 3969 / j.issn.1671-7856. 2022. 04. 010
中文关键词:  自身免疫性脑脊髓炎  髓鞘修复  阿托伐他汀  RhoA/ ROCK-1 通路
英文关键词:autoimmune encephalomyelitis  myelin repair  atorvastatin  RhoA/ ROCK-1 pathway
基金项目:
作者单位E-mail
张沁丽 长治医学院附属和平医院神经内科,山西 长治 046000 shengmingkx2020@ 163.com 
王玉芬 长治医学院附属和平医院神经内科,山西 长治 046000 3385314799@ qq.com 
刘 红 长治医学院附属和平医院神经内科,山西 长治 046000  
刘博雯 长治医学院附属和平医院神经内科,山西 长治 046000  
摘要点击次数: 78
全文下载次数: 31
中文摘要:
       目的 探讨阿托伐他汀对自身免疫性脑脊髓炎(EAE)小鼠髓鞘修复及 RhoA/ Rock1 通路的影响。 方法 采用 MOG35-55 免疫建立 EAE 小鼠模型,小鼠随机分为空白组、模型组、阿托伐他汀组、高脂饮食组、高脂饮食+阿托伐他汀组,每组 6 只,阿托伐他汀每只小鼠每天按 0. 5 mL 混悬液灌服,连续 28 d。 各组小鼠神经功能评分,采用苏木精-伊红(HE)、固蓝(LFB)染色、透射电镜及免疫组化染色方法检测各组小鼠脊髓组织炎症反应、髓鞘脱失及髓鞘再生情况;酶联免疫吸附法(ELISA)检测小鼠血清中肿瘤坏死因子-α(TNF-α)、白介素-6( IL-6)、一氧化氮(NO)的表达;蛋白免疫印迹(Western blot)法检测脑组织 RAS 同源基因家族成员 A(RhoA)、Rho 相关蛋白激酶 1(Rock1)蛋白表达;实时荧光定量 PCR(qRT-PCR)检测脊髓组织硫酸软骨素蛋白多糖(NG2)、髓鞘碱性蛋白 (MBP)及脑组织 RhoA、Rock1 mRNA 表达。 结果 与空白组比较,模型组小鼠见较多炎性细胞浸润、发生明显脱髓鞘改变、部分髓鞘崩解、断裂、脱失;模型小鼠血清中 TNF-α、IL-6、NO 的含量及脑组织 RhoA、Rock1 蛋白和 mRNA 表达均明显升高(P<0. 01),脊髓组织 NG2、MBP 蛋白及 mRNA 表达明显降低(P<0. 01)。 与模型组比较,阿托伐他汀组小鼠见极少量炎性细胞浸润、脱髓鞘程度明显好转,明显降低小鼠血清中 TNF-α、IL-6、NO 的含量及脑组织 RhoA、Rock1 蛋白和 mRNA 表达(P<0. 05),明显升高 MBP、NG2 蛋白和 mRNA 表达(P<0. 05);高脂饮食+阿托伐他汀组明显降低小鼠神经功能评分、脑组织 RhoA、Rock1 蛋白表达,明显升高 NG2 mRNA 表达。 结论 阿托伐他汀能改善 EAE 小鼠炎性细胞浸润及脱髓鞘程度,降低高脂饮食 EAE 小鼠神经功能评分,其中作用机制可能与调节 RhoA/ Rock1 通路改善脱髓鞘程度,从而发挥对 EAE 小鼠的治疗作用有关。
英文摘要:
       Objective To investigate the effect of atorvastatin on myelin repair and the RhoA/ Rock1 pathway in mice with autoimmune encephalomyelitis (EAE). Methods MOG35-55 immunization was used to establish an EAE mouse model. The mice were randomly divided into the control group, model group, atorvastatin group, high fat diet group and high fat diet+atorvastatin group ( n= 6 per group). The atorvastatin was administered to each mouse daily by 0. 5 mL suspension, for 28 consecutive days. Mice were scored for neurological function and clinical symptoms were observed. Hematoxylin-eosin ( HE ) staining, Luxol fast blue ( LFB ) staining, transmission electron microscopy and immunohistochemical staining method were used to detect inflammation and demyelination and remyelination of the spinal cord tissue of each group of mice. The expression of tumor necrosis factor-α (TNF-α), interleukin-6 ( IL-6) and nitric oxide (NO) in serum was detected by enzyme linked immunosorbent assay (ELISA); protein immanoblotting assay(Western blot) method was used to detect the expression of Ras homologous gene family member A (RhoA) and Rho associated protein kinase 1 (ROCK1) in brain tissue. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression of chondroitin sulfate proteoglycan ( NG2) and myelin basic protein ( MBP) in spinal cord and RhoA and Rock1 mRNA expression in brain tissue. Results Compared with the control group, the model group showed more inflammatory cell infiltration, marked demyelination, partial myelination disintegration, breakage and demyelination; TNF-α, IL-6 and NO in serum and the expression of RhoA, Rock1 protein and mRNA in brain tissue were significantly increased, while the expression levels of NG2 and MBP protein and mRNA in spinal cord tissue were significantly decreased (P<0. 01). Compared with the model group, the atorvastatin group showed significant improvement in inflammatory cell infiltration and demyelination, significantly decreased TNF-α, IL-6 and NO in serum, expression of RhoA and Rock1 protein and mRNA in brain tissue and increased expression of MBP, NG2 protein and mRNA in brain tissue (P< 0. 05). The high fat diet + atorvastatin group showed significantly decreased neurological function scores, brain tissue RhoA and Rock1 expression and significantly increased NG2 mRNA expression. Conclusions Atorvastatin improved inflammatory cell infiltration and demyelination in EAE mice and reduced neurological function scores in EAE mice on a high fat diet. The mechanism of action may be related to the regulation of the RhoA/ Rock1 pathway to improve the degree of demyelination and thus exert a therapeutic effect on EAE mice.
查看全文  查看/发表评论  下载PDF阅读器
关闭
您是第 5790365 位访问者
版权所有:中国实验动物学会 主管单位:中国科学技术协会 主办单位:中国实验动物学会 中国医学科学院医学实验动物研究所
地  址: 北京市朝阳区潘家园南里5号 邮编:100021 电话:010-67779337 E-mail:bjb@cnilas.org
本系统由北京勤云科技发展有限公司设计
微信关注二维码