摘要
目的探究上感颗粒改善流感病毒感染小鼠肺部炎症反应的作用机制。方法经鼻腔接种H1N1流感病毒建立流感病毒肺部感染小鼠模型。实验分为正常对照组、模型组、阳性对照组和低、中、高剂量上感颗粒组,治疗7 d。记录小鼠的死亡情况,试验结束后测定小鼠体质量和肺湿重。苏木精/伊红(HE)染色观察小鼠肺组织的病理组织形态,酶联免疫吸附试验检测肺组织肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-8和转化生长因子-β(TGF-β)水平,试剂盒法检测肺组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)含量,实时荧光定量PCR检测Toll样受体4(TLR4)/核因子-κB(NF-κB)炎症信号通路。蛋白免疫印迹检测TANK结合激酶1(TBK1)/干扰素调节因子(IRFs)信号通路。结果与模型组相比,上感颗粒和磷酸奥司他韦均降低了流感病毒H1N1感染小鼠肺湿重(P<0.05,P<0.001),减少了肺组织炎性细胞浸润,降低了炎症因子TNF-α、IL-6、IL-8和TGF-β的水平(P<0.05,P<0.01,P<0.001),降低了肺组织SOD和GSH-Px的水平(P<0.05,P<0.01),提高了MDA水平(P<0.05,P<0.01)。此外,抑制了TLR4、MyD88和p38的mRNA水平(P<0.05,P<0.01)和TBK1/IRF3/7/NF-κB信号通路的蛋白表达(P<0.05,P<0.01,P<0.001)。结论上感颗粒能有效减轻流感小鼠肺损伤、肺部炎症和氧化应激,其机制可能与下调TLR4/NF-κB炎症信号通路有关。
Objective To explore the mechanism of Shanggan granules in suppressing pulmonary inflammation in mice infected with H1N1 influenza virus.MethodsA mouse model of pulmonary influenza virus infection was established by nasal inoculation with H1N1 influenza virus.Mice were divided into a normal control group,model group,positive control group,and low-,medium-,and high-dose Shanggan granules groups.Mice were treated for 7 days and then sacrificed,and the body weight and lung wet weight were measured.Pathological changes in the lung tissues were detected by hematoxylin/eosin(HE)staining.Tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-8,and transforming growth factor-β(TGF-β)levels in lung tissues were detected by enzyme-linked immunosorbent assay,and superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)were detected using appropriate kits.Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)inflammatory signaling pathways were detected by real-time polymerase chain reaction,and TANK-binding kinase 1(TBK1)/interferon regulatory factor(IRF)signaling pathway proteins were detected by Western blot.ResultsBoth Shanggan granules and oseltamivir phosphate reduced the lung wet weight(P<0.05,P<0.001)in mice infected with influenza virus H1N1 compared with the model group,decreased the infiltration of inflammatory cells in lung tissue,reduced levels of the inflammatory factors TNF-α,IL-6,IL-8,and TGF-β(P<0.05,P<0.01,P<0.001),decreased levels of SOD and GSH-Px in lung tissue(P<0.05,P<0.01),and increased MDA levels(P<0.05,P<0.01).Shanggan granules and oseltamivir phosphate also reduced TLR4,MyD88,and p38 mRNA levels(P<0.05,P<0.01)and expression of TBK1/IRF3/7/NF-κB signaling pathway proteins(P<0.05,P<0.01,P<0.001).Conclusions Shanggan granules may effectively reduce lung injury,lung inflammation,and oxidative stress,via a mechanism related to the down-regulation of TLR4/NF-κB inflammatory signaling pathways.
作者
李茂
郭志洪
刘林洁
张梦楠
李修元
LI Mao;GUO Zhihong;LIU Linjie;ZHANG Mengnan;LI Xiuyuan(Department of Respiratory Medicine,Affiliated Hospital of Traditional Chinese Medicine,Southwest Medical University,Luzhou 646000,China;Department of Respiratory Medicine,Sichuan Second Hospital of Traditional Chinese Medicine,Chengdu 610031)
出处
《中国比较医学杂志》
北大核心
2025年第8期58-66,共9页
Chinese Journal of Comparative Medicine
基金
四川省中医药管理局(2020JC0152)。
作者简介
李茂(1990-),女,硕士,主治医师,研究方向:中西结合防治呼吸系统疾病。E-mail:1072899055@qq.com;通信作者:李修元(1986-),男,硕士,主治医师,研究方向:中西结合防治呼吸系统疾病。E-mail:lxy19860210@163.com。
