西维来司钠对实验性自身免疫性脑脊髓炎模型大鼠的保护作用 点击下载
论文标题: 西维来司钠对实验性自身免疫性脑脊髓炎模型大鼠的保护作用
英文标题:
中文摘要: 目的:研究西维来司钠对实验性自身免疫性脑脊髓炎(EAE)模型大鼠的保护作用。方法:取Wistar大鼠60只,随机分为正常对照(生理盐水)组、模型(生理盐水)组、阳性药物[醋酸泼尼松片5 mg/(kg·d)]组和西维来司钠低、中、高剂量[5、8、10         mg/(kg·d)]组,每组10只。除正常对照组不作处理外,其余各组大鼠均以全脊髓匀浆作为免疫抗原建立EAE模型,建模当天开始ip给予相应药物,连续16 d。对各组大鼠神经功能进行评分,观察其脑和脊髓组织病理学变化,检测其外周血中干扰素γ(IFN-γ)、白细胞介素4(IL-4)、巨噬细胞炎性蛋白1α(CCL3)和调节活化正常T细胞表达与分泌的趋化因子(CCL5)的含量。结果:与正常对照组比较,模型组大鼠的神经功能评分和IFN-γ、CCL3、CCL5含量增加,IL-4含量降低(P<0.01),组织呈现髓鞘脱失和炎性细胞浸润。与模型组比较,阳性药物组和西维来司钠低、中、高剂量组大鼠的神经功能评分和CCL3、CCL5含量降低(P<0.01),脱髓鞘改变和炎性细胞浸润均减轻,阳性药物组和西维来司钠高剂量组大鼠的IFN-γ含量降低、IL-4含量增加,西维来司钠中剂量组大鼠IL-4含量增加(P<0.01),其余各组差异无统计学意义(P>0.05)。上述效果均呈剂量依赖性。结论:西维来司钠能有效减轻EAE模型大鼠髓鞘脱失和炎症细胞浸润,其机制可能与减少外周血中IFN-γ含量、增加IL-4含量、抑制CCL3和CCL5表达有关。
英文摘要: OBJECTIVE: To study the protective effect of sivelestat sodium on experimental autoimmune encephalomyelitis (EAE) model rats. METHODS: 60 Wistar rats were randomly divided into normal control group (normal saline), model group (normal saline), positive drug group [prednisone acetate tablets 5 mg/(kg·d)] and sivelestat sodium low-dose, middle-dose and high-dose groups [5, 8, 10 mg/(kg·d)] with 10 rats in each group. Except for normal control group, other groups were given guinea pig spinal cord homogenate as antigen to produce EAE model, and then given relevant medicine ip since the same day of modeling, for consecutive 16 d. The neurologic function of mice was scored, and pathological changes of brain and spinal cord were observed; the content of IFN-γ, IL-4, CCL3, chemotactic factor CCL5 regulating and activating normal T cell expression and secretion were determined. RESULTS: Compared with normal control group, neurological function score and the content of IFN-γ, CCL5 and CCL3 increased, while IL-4 content decreased (P<0.01); myelinoclasis and inflammatory cell infiltration occurred. Compared with model group, neurological function score and the content of CCL3 and CCL5 decreased in positive drug group and sivelestat sodium low-concentration, medium-concentration and high-concentration groups (P<0.01); both myelinoclasis and inflammatory cell infiltration relieved; the content of IFN-γ decreased, while IL-4 content increased in positive drug group and sivelestat sodium high-concentration group; IL-4 content increased in sivelestat sodium medium-concentration group (P<0.01); there was no statistical significance in other groups (P>0.05). Above effect depended on drug dose. CONCLUSIONS: Sivelestat sodium can relieve myelinoclasis and inflammatory cell infiltration, and the mechanism may be related to the decrease of IFN-γ content, the increase of IL-4 content, and inhibition of CCL3 and CCL5 expression in peripheral blood.
期刊: 2016年第27卷第7期
作者: 周游,张伶姝,杨元,张淑江,李作孝
英文作者: ZHOU You,ZHANG Lingshu,YANG Yuan,ZHANG Shujiang,LI Zuoxiao
关键字: 西维来司钠;实验性自身免疫性脑脊髓炎;大鼠;干扰素γ;白细胞介素4;巨噬细胞炎性蛋白1α
KEYWORDS: Sivelestat sodium; Experimental autoimmune encephalomyelitis; Rat; IFN-γ; IL-4; CCL3
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