摘要
目的:探讨槲皮素对肺结核小鼠Toll样受体4 (Toll-like receptor 4,TLR4)、肿瘤坏死因子相关因子-6 (Tumor necrosis factor receptor-associated factor 6,TRAF6)、白细胞介素-1β(Interleukin-1β,IL-1β)表达的影响。方法:120只昆明系雌性小鼠,随机选取15只为空白组,其余105只建立肺结核病小鼠模型。选取模型制备成功的60只小鼠分为模型组、槲皮素低、中、高剂量组,每组15只,低、中、高剂量组分别灌胃0.4 mL浓度分别为1 mg/mL,2.5 mg/mL,5 mg/mL的槲皮素,空白组及模型组给予等量PBS,于给药8天后,检测各组小鼠体征变化,HE染色观察肺脏病理变化,用免疫组织化学法,蛋白免疫印迹法和实时荧光定量检测肺脏组织TLR4、TRAF6、IL-1β表达水平。结果:与空白组比较,模型组小鼠皮毛暗淡无光,精神萎靡,懒动,且体质量增加量显著下降(P <0.05),肺脏炎症明显增加,TLR4、TRAF6、IL-1β蛋白及m RNA表达量显著上升(P <0.05);与模型组比较,槲皮素各剂量组能显著改善小鼠皮毛及精神状态,且体质量增加量显著增加(P <0.05),肺脏炎症明显改善;TLR4、TRAF6、IL-1β蛋白及mRNA表达量显著下调(P <0.05),且呈现药物剂量依赖性(P <0.05)。结论:槲皮素可明显减轻肺结核病造成的肺脏炎症反应,推测其机制为槲皮素抑制TLR4、TRAF6的高表达,阻碍相关炎症信号通路激活从而减少相关炎症因子的释放,抑制炎症反应,减轻组织病理损伤,起免疫调节抗感染作用。
Objective:To discuss the effect of quercetin on expressions of toll-like receptor 4(TLR4),tumor necrosis factor receptor-associated factor 6(TRAF6)and Interleukin-1β(IL-1β)in mice with tuberculosis.Methods:Among 120 Kunming male mice,15 mice were selected as the blank group randomly,and the other 105 mice were used to establish models of tuberculosis.Select 60 mice which succeeded in establishing models were divided into the model group,the groups of quercetin in low,middle and high doses,15 mice in each group.The groups of quercetin in low,middle and high doses received 0.4 mL of quercetin in 1 mg/mL,2.5 mg/mL and 5 mg/mL by gavage respectively,while the blank group and the model group received equivalent PBS.After medication for 8 days,detected the changes of physical signs of mice in each group,observed pathological changes of the lung via HE staining,and detected the expression levels of TLR4,TRAF6 and IL-1βin lung tissue via immunohistochemistry,Western blot and real-time quantitative PCR.%Results:Comparing with the blank group,such physical signs as dull fur,low spirits and lassitude appeared in mice in the model group,the increase in body mass was significantly reduced(P<0.05),the pulmonary inflammatory reactions were significantly increased,and the protein and mRNA expression levels of TLR4,TRAF6 and IL-1βwere significantly increased(P<0.05).Comparing with the model group,the fur and state of mind in mice in the groups of quercetin in each dose were improved,the increase in body mass was significantly raised(P<0.05),the pulmonary inflammatory reactions were significantly improved,and the protein and mRNA expression levels of TLR4,TRAF6 and IL-1βwere significantly decreased(P<0.05),which appeared dose-dependent(P<0.05).Conclusion:Quercetin can significantly relieve the pulmonary inflammatory reactions induced by tuberculosis.In terms of its functional mechanism,it is speculated that quercetin inhibits the high expressions of TLR4,TRAF6 and IL-1β,hinder the activation of relevant inflammatory signal pathways to reduce the release of relevant inflammatory factors,suppress inflammatory reactions and alleviate pathological injury in tissue,thus to exert effect in immunoregulation and anti-inflammation.
作者
陈振宇
缪利娅
朱银超
CHEN Zhenyu;MIAO Liya;ZHU Yinchao
出处
《新中医》
CAS
2019年第10期8-13,共6页
New Chinese Medicine
作者简介
陈振宇(1982-),男,主管药师,主要从事药理学研究。
