异甘草素对实验性自身免疫性神经炎大鼠模型的影响及机制研究  

Effects of isoliquiritigenin on experimental autoimmune neuritis in rats and its mechanism

作　　者：何谷芬[1] 符婉 肖子建 HE Gufen;FU Wan;XIAO Zijian(Dept.of Neurology,the First Affiliated Hospital of University of South China,Hengyang 421001,China)

机构地区：[1]南华大学附属第一医院神经内科,湖南衡阳421001

出　　处：《华夏医学》2023年第5期16-23,共8页Acta Medicinae Sinica

基　　金：湖南省自然科学青年基金项目(2019JJ50551);衡阳市科技计划指导项目(hkf201947221)。

摘　　要：目的:观察异甘草素(ISL)对大鼠实验性自身免疫性神经炎(EAN)的影响并探讨机制。方法:足底注射P257-81多肽建立EAN大鼠模型,免疫后1 h,每天腹腔注射ISL(60 mg/kg)溶液,共14 d。观测大鼠发病情况,运用HE染色及透射电镜观察坐骨神经结构,ELISA法检测血清中炎症因子水平,Western blot检测脾脏单核巨噬细胞中诱导型一氧化氮合酶(iNOS)和精氨酸酶1(Arg1)、信号转导及转录激活因子3(STAT3)包括t⁃STAT3和p⁃STAT3的蛋白表达。结果:与EAN组比较,EAN+ISL组大鼠行为评分显著降低,体重明显增加,坐骨神经中炎症细胞浸润数明显减少,坐骨神经的脱髓鞘现象明显减少,血清中白介素⁃1β(IL⁃1β)、肿瘤坏死因子⁃α(TNF⁃α)、白介素⁃6(IL⁃6)和干扰素⁃γ(IFN⁃γ)水平明显降低,脾脏单核巨噬细胞中iNOS蛋白表达显著下调,Arg1表达显著上调,p⁃STAT3蛋白表达及p⁃STAT3/t⁃STAT3比值均明显降低(P<0.05)。结论:ISL对EAN具有抑制作用,其机制可能与调控STAT3⁃巨噬细胞极化途径有关。Objective:To observe the effects of isoliquiritigenin(ISL)on experimental autoimmune neuritis(EAN)in rats and to explore its possible mechanism.Methods:Male specific pathogen free(SPF)Lewis rats were injected P257⁃81 polypeptide through plantar injection to establish an EAN model.The solution of ISL(60 mg/kg)was injected intraperitoneally every day for 14 days after 1 h immunization.The structure of sciatic nerve of rats was observed by HE staining and transmission electron microscopy.The levels of inflammatory factors in serumof rats were detected by ELISA.The protein expressions of inducible nitric oxide synthase(iNOS),arginase 1(Arg1),signal transduction and activator of transcription 3(STAT3)including t⁃STAT3 and p⁃STAT3 in spleen mononuclear macrophages of rats were tested by Western blot.Results:Compared with EAN model group,the behavioral scores of rats was significantly reduced,body weight of rats was significantly increased,the number of inflammatory cells infiltrating in the sciatic nerve of rats was significantly reduced,the demyelination of the sciatic nerve of rats was significantly reduced,the levels of serum interleukin⁃1β(IL⁃1β),tumor necrosis factor⁃α(TNF⁃α),interleukin⁃6(IL⁃6)and interferon⁃γ(IFN⁃γ)of rats were significantly reduced.At the same time,the protein expression of iNOS in spleen mononuclear macrophages of rats was significantly down⁃regulated,while the protein expression of Arg1 was significantly up⁃regulated.Moreover,the protein expression of p⁃STAT3 and the ratio of p⁃STAT3 to t⁃STAT3 were significantly decreased in EAN+ISL group(P<0.05).Conclusion:ISL inhibits EAN,and the mechanism may be related to the regulation of STAT3⁃macrophage polarization pathway.

关 键 词：异甘草素 实验性自身免疫性神经炎 大鼠 巨噬细胞极化 信号转导及转录激活因子3 

分 类 号：R745.43[医药卫生—神经病学与精神病学]