马索罗酚对实验性自身免疫性脑脊髓炎小鼠血脑屏障的保护作用及机制研究

发布时间：2018-09-11 20:03

【摘要】：目的探究马索罗酚(NDGA)对实验性自身免疫性脑脊髓炎(EAE)小鼠血脑屏障的保护作用及其机制。方法将27只C57BL/6小鼠随机分为正常组、EAE组与NDGA组,应用MOG35-55诱导EAE模型。小鼠发病后神经功能评分达1分时开始给予NDGA组NDGA 10 mg(/kg·d)腹腔注射,EAE组及正常对照组给予5%DMSO 10 ml/(kg·d)腹腔注射。给药20 d后比较各组小鼠神经功能评分,应用荧光显微镜观察伊文斯兰染色后各组小鼠血脑屏障通透性改变情况,激光共聚焦显微镜观察各组小鼠claudin-5、occludin、ZO-1表达情况,Real-time PCR检测各组小鼠NF-κB及MMP-9 mRNA水平。结果与正常对照组相比,EAE组伊文斯兰染色后荧光漏出范围较大,紧密连接蛋白连续性遭到破坏,NF-κB、MMP-9 mRNA水平均上调;与EAE组相比,NDGA组神经功能评分显著降低(P0.05),伊文斯兰染色后荧光范围较小且强度较弱,紧密连接蛋白连续性破坏减轻,NF-κB、MMP-9 mRNA水平下调(P0.05)。结论马索罗酚可以保护EAE小鼠血脑屏障免遭破坏,延缓疾病进展,其机制可能是保护紧密连接蛋白完整性以及抑制MMP-9、NF-κB表达。
[Abstract]:Objective To investigate the protective effect of massolol (NDGA) on blood-brain barrier (BBB) in experimental autoimmune encephalomyelitis (EAE) mice and its mechanism.Methods Twenty-seven C57BL/6 mice were randomly divided into normal group, EAE group and NDGA group.The EAE model was induced by MOG35-55.The neurological function score of the mice was 1 minute after onset. Intraperitoneal injection, intraperitoneal injection of 5% DMSO 10 ml / (kg Results Compared with the normal control group, the fluorescence leakage range of EAE group was larger, the continuity of tight junction protein was destroyed, and the levels of NF-kappa B and MMP-9 mRNA were up-regulated in EAE group. Compared with EAE group, the neurological function score of NDGA group was significantly lower (P 0.05), and the fluorescence of Evans blue staining was up-regulated. Conclusion Masoprolol can protect the blood-brain barrier from damage and delay the progression of the disease in EAE mice. The mechanism may be to protect the integrity of tight junction protein and inhibit the expression of MMP-9 and NF-kappa B.
【作者单位】：河北医科大学第二医院神经内科河北省神经病学重点实验室;
【基金】：国家自然科学基金(81100884)
【分类号】：R744.51

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