首页|黄芪多糖通过NF-κB/IRF-3/IRF-7轴对自身免疫性炎性肌病大鼠免疫功能及炎性症状作用的研究

黄芪多糖通过NF-κB/IRF-3/IRF-7轴对自身免疫性炎性肌病大鼠免疫功能及炎性症状作用的研究

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目的 探讨黄芪多糖对自身免疫性炎性肌病大鼠免疫功能及炎性症状的作用及其可能的作用机制。方法 构建自身免疫性炎性肌病大鼠模型,随机分为模型组、黄芪多糖低剂量组、黄芪多糖高剂量组(以下简称低剂量组、高剂量组)、阳性对照组,另设正常组。低剂量组、高剂量组分别灌胃黄芪多糖15、30 mL·kg-1·d-1,阳性对照组灌胃甲基泼尼松龙5。4 mL·kg-1·d-1,模型组和对照组灌胃等体积生理盐水,连续干预1个月。观察大鼠免疫后的一般状态;苏木素-伊红(hematoxylin-eosin,HE)染色观察大鼠骨骼肌的病理变化;酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测炎症细胞因子和免疫细胞因子的水平;全自动生化仪检测血清激酶指标;蛋白印记法(Western blotting)检测信号通路蛋白的表达量。结果 模型组大鼠骨骼肌损伤严重,存在明显间质病变,较大量炎症细胞浸润,骨骼肌肌细胞核内移;与模型组比较,低剂量组、高剂量组大鼠病理明显改善,低剂量组仍存在一定程度的间质水肿和炎症细胞浸润,高剂量组和阳性对照组间质水肿、炎症细胞浸润以及细胞核内移明显减轻。模型组、低剂量组、高剂量组、阳性对照组和正常组比较,大鼠血清肌酸激酶(creatine kinase,CK)、乳酸脱氢酶(lactic dehydrogenase,LDH)和羟丁酸转移酶(hydroxybutyric acid dehydrogenase,HBDH)水平逐渐降低,血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素(interleukin,IL)-6水平逐渐降低,IL-4水平逐渐降低,干扰素-γ(interferon-γ,INF-γ)水平逐渐升高(P<0。05);模型组、低剂量组、高剂量组和正常组比较,大鼠骨骼肌磷酸化核因子κB p65(phosphorylated nuclear factor κB p65,p-NF-κB p65)、干扰素调节因子(interferon regulatory factor,IRF)-3和IRF-7蛋白表达量逐渐降低(P<0。05)。结论 黄芪多糖对自身免疫性炎性肌病大鼠有调节免疫功能、减轻炎性症状的作用,其作用机制可能与抑制NF-κB/IRF-3/IRF-7轴有关。
Study on the effect of astragalus polysaccharides on the immune function and inflammatory symptoms in rats with autoimmune inflammatory myopathy through NF-κB/IRF-3/IRF-7 axis
Objective To explore the effects of astragalus polysaccharides on the immune function and inflammatory symptoms in rats with autoimmune inflammatory myopathy and its possible mechanism.Methods A rat model of autoimmune inflammatory myopathy was constructed and randomly divided into model group,low-dose astragalus polysaccharide group,high-dose astragalus polysaccharide group(hereinafter referred to as low-dose group and high-dose group),positive control group,and a normal group.The low-dose group and high-dose group were given 15 and 30 mL·kg-1·d-1 astragalus polysaccharides,respectively.The positive control group were given 5.4 mL·kg-1·d-1 methylprednisolone,while the model group and control group were given equal volume of distilled water for 1 month.The general state of rats after immunization was observed.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of rat skeletal muscle.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of inflammatory and immune cytokines.Serum kinase index was detected by automatic biochemical analyzer.The expression of signaling pathway protein was detected by Western blotting.Results The skeletal muscles of the rats in the model group were severely injured,with obvious interstitial lesions,a large amount of inflammatory cell infiltration,and skeletal muscle cell nuclei moved inward.Compared with the model group,the pathology of the rats in the administration group was significantly improved:the low-dose group still had a certain degree of interstitial edema and inflammatory cell infiltration.In the high-dose group and the positive control group,the interstitial edema,inflammatory cell infiltration and cell nucleus infiltration were significantly reduced.In the model group,low-dose group,high-dose group,positive control group and normal group,the serum creatine kinase(CK),lactic dehydrogenase(LDH)and hydroxybutyric acid dehydrogenase(HBDH)levels of rats gradually decreased,the serum tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels gradually decreased,the interleukin-4(IL-4)level gradually decreased,and the interferon-γ(INF-γ)level gradually increased(P<0.05).In the model group,low-dose group,high-dose group and normal group,the protein expression of phosphorylated nuclear factor kappa B p65(p-NF-κB p65),interferon regulatory factor-3(IRF-3)and IRF-7 in rat skeletal muscle gradually decreased(P<0.05).Conclusion Astragalus polysaccharides can regulate immune function and reduce inflammatory symptoms in rats with autoimmune inflammatory myopathy.Its mechanism of action may be related to the inhibition of NF-κB/IRF-3/IRF-7 axis.

astragalus polysaccharideautoimmune inflammatory myopathyimmune functioninflammatory symptomsnuclear factor κB/interferon regulatory factor-3/interferon regulatory factor-7 axis

江万清、张宗芳、陈增华

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邯郸中心医院皮肤科,邯郸 056001

沧州市中心医院风湿免疫科,沧州 061000

衡水市第四人民医院检验科,衡水 053000

黄芪多糖 自身免疫性炎性肌病 免疫功能 炎性症状 核因子κB/干扰素调节因子-3/干扰素调节因子-7轴

河北省2021年医学科学研究课题计划项目

20211293

2024

西北药学杂志
西安交通大学,陕西省药学会

西北药学杂志

CSTPCD
影响因子:0.912
ISSN:1004-2407
年,卷(期):2024.39(5)