刺糖多糖调控Toll样受体4对免疫抑制活性的影响  

Effect ofAlhagi honey polysaccharide on immunosuppressive activity by regulating Toll-like receptor 4

作　　者：吕志远 宋建忠 曲真真 李进发 李改茹[1] 常军民[1,3] LYU Zhi-yuan;SONG Jian-zhong;QU Zhen-zhen;LI Jin-fa;LI Gai-ru;CHANG Jun-min(College of Pharmacy,Xinjiang Medical University,Urumqi 830000,China;Department of Pharmacy,Affiliated Tumor Hospital of Xinjiang Medical University,Urumqi 830011,China;Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology,Urumqi 830000,China)

机构地区：[1]新疆医科大学药学院,乌鲁木齐830000 [2]新疆医科大学附属肿瘤医院药学部,乌鲁木齐830011 [3]新疆天然药物活性组分与释药技术重点实验室,乌鲁木齐830000

出　　处：《天然产物研究与开发》2024年第8期1393-1400,1384,共9页Natural Product Research and Development

基　　金：国家自然科学基金(82060756)。

摘　　要：揭示刺糖多糖对Toll样受体4(Toll-like receptor 4,TLR4)的调控机制。构建C57BL/6J免疫抑制小鼠模型及TAK-242抑制剂诱导的RAW 264.7模型,小鼠模型给予刺糖多糖组800 mg/kg以及RAW 264.7模型给予不同浓度的刺糖多糖(25、50、75、100μg/mL)进行干预。酶联免疫吸附测定法(enzyme-linked immunosorbent assay,ELISA)分别测定小鼠血清中细胞因子、RAW 264.7细胞因子分泌水平。蛋白免疫印迹(Western blot)与实时荧光定量PCR(real-time quantitative PCR,qRT-PCR)法检测TLR4和髓样分化因子88(myeloiddifferentiationfactor88,MyD88)与肿瘤坏死因子相关的分子6(TNF receptor associated factor 6,TRAF6)在相关组织和细胞中的表达。结果表明刺糖多糖显著提高了免疫抑制小鼠的脾脏指数、胸腺指数,以及血清中白细胞介素-2(interleukin-2,IL-2)、白细胞介素-4(interleukin-4,IL-4)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、免疫球蛋白G(Immunoglobulin G,IgG)和免疫球蛋白M(Immunoglobulin M,IgM)的含量。在TAK-242抑制剂诱导的细胞模型中,刺糖多糖增加了白细胞介素-1β(Interleukin-1β,IL-1β)、白细胞介素-6(Interleukin-6,IL-6)、白细胞介素-12(interleukin-12,IL-12)、TNF-α、核因子κB(nuclear factor-κB,NF-κB)的分泌。此外,刺糖多糖逆转了TLR4和MyD88/TRAF6的表达下调。刺糖多糖可以通过调节MyD88途径激活TLR4受体的免疫应答。This study elucidates the regulatory mechanism of Alhagi honey polysaccharide on Toll-like receptor 4(TLR4).An immunosuppressive mouse model was established using C57BL/6J mice,and a RAW 264.7 model induced by TAK-242 inhibitor was constructed.In the mouse model,Alhagi honey polysaccharide were administered at 800 mg/kg,while the RAW 264.7 model received interventions with different concentrations of Alhagi honey polysaccharide(25,50,75,100μg/mL).Enzyme-linked immunosorbent assay(ELISA)was employed to measure cytokine levels in mouse serum and RAW 264.7 cell culture supernatant.Protein immunoblotting and real-time quantitative PCR(qRT-PCR)were conducted to detect the expression of TLR4,myeloid differentiation factor 88(MyD88),and tumor necrosis factor-αreceptor associated factor 6(TRAF6)in relevant tissues and cells.Results indicate that Alhagi honey polysaccharide significantly increased the spleen index,thymus index,and serum levels of interleukin-2(IL-2),interleukin-4(IL-4),tumor necrosis factor-α(TNF-α),immunoglobulin G(IgG),and immunoglobulin M(IgM)in immunosuppressive mice.In the TAK-242 inhibitor-induced cell model,Alhagi honey polysaccharide increased the secretion of interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-12(IL-12),TNF-α,and nuclear factor-κB(NF-κB).Furthermore,Alhagi honey polysaccharide reversed the downregulation of TLR4 and MyD88/TRAF6 expression.Alhagi honey polysaccharide can activate the immune response of TLR4 receptors by modulating the MyD88 pathway.

关 键 词：刺糖多糖 TOLL样受体4 巨噬细胞RAW 264.7 免疫抑制 

分 类 号：R967[医药卫生—药理学]