[关键词]
[摘要]
目的 研究复方银花解毒颗粒(Compound Yinhua Jiedu Granule)对脂多糖(lipopolysaccharide,LPS)致幼龄大鼠急性肺炎模型的抗炎作用及Toll样受体4(Toll like receptor 4,TLR4)/核转录因子-κB(nuclear factor-κB,NF-κB)/NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)信号通路的影响。方法 将120只幼龄大鼠随机分为6组,分别为对照组、模型组、布洛芬颗粒组(0.8 g/kg)及复方银花解毒颗粒低、中、高剂量(1.25、2.5、5 g/kg)组,ig给药1周,末次给药1 h后尾iv LPS(1 mg/kg)制备急性肺炎模型,6 h后采用麻醉后颈椎脱臼处死。采用ELISA试剂盒检测各组大鼠肺泡灌洗液及血清中炎症因子白细胞介素-1β(interleukin-1β,IL-1β)、IL-17、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平的变化;HE染色观察肺组织形态学变化;运用免疫组化染色法检测肺组织TLR4,入核NF-κB和NLRP3蛋白的表达,Western blotting法检测肺组织中TLR4、磷酸化NF-κB(p-NF-κB)、磷酸化核转录因子-κB抑制蛋白α(nuclear factor-κB inhibitor protein α,p-IκBα)和NLRP3蛋白的表达。结果 复方银花解毒颗粒预处理对LPS诱导幼龄大鼠急性肺损伤具有较强的保护作用,可降低模型大鼠肺泡灌洗液及血清中炎症因子IL-1β、IL-17、TNF-α的水平,减少肺组织中TLR4、NF-κB的激活和NLRP3蛋白的表达。结论 复方银花解毒颗粒对LPS致幼龄大鼠急性肺炎模型具有抗炎作用,其机制可能与下调TLR4/NF-κB/NLRP3炎症信号通路有关。
[Key word]
[Abstract]
Objective To study the anti-inflammatory effect of Compound Yinhua Jiedu Granules (复方银花解毒颗粒) and on lipopolysaccharide (LPS) induced acute pneumonia in juvenile rats the effect of TLR4/NF-κB/NLRP3 signaling pathway. Methods A total of 120 juvenile rats were randomly divided into six groups: normal control group, model group, Ibuprofen granule group (0.8 g/kg), and Compound Yinhua Jiedu Granules low-dose group, medium-dose group, high dose group (1.5, 2.5, and 5 g/kg). The drug was ig preadministered for one week, and LPS (1 mg/kg) was injected into the tail vein 1 h after the last administration to prepare the acute pneumonia model, than the animals was sacrificed by cervical dislocation after anesthesia 6 h later. The inflammatory factors interleukin-1β (IL-1β), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α) level change in alveolar lavage fluid and serum of mice in each group were detected by ELISA kit, at the same time, the changes of lung histopathology were observed by HE staining. The protein expression of TLR4, the nuclear NF-κB and NLRP3 in lung tissues were detected by immunohistochemical staining. The protein expression of TLR4, phosphorylated NF-κB (p-NF-κB), phosphorylated IκBα (p-IκBα), and NLRP3 in lung tissues were detected by Western blotting. Results The preadministration of Compound Yinhua Jiedu Granules had a strong protective effect on LPS-induced acute lung injury in juvenile rats, reduced the inflammatory factors IL-1β, IL-17, and TNF-α in juvenile rats alveolar lavage fluid and serum, and decreased the avtivation of TLR4, NF-κB and the expression NLRP3 in lung tissues. Conclusion The anti-inflammatory protective effect of Compound Yinhua Jiedu Granules on LPS-induced acute pneumonia in juvenile rats may be related to the down-regulation of the TLR4/ NF-κB /NLRP3 inflammatory signaling pathway.
[中图分类号]
R285
[基金项目]