迷迭香酸调节Toll样受体4/核因子-κB信号通路对急性中耳炎大鼠炎症反应的影响  

Impacts of rosmarinic acid on inflammatory response in rats with acute otitis media by regulating TLR4/NF-κB signaling pathway

作　　者：孙饶奚 唐文松[1] SUN Raoxi;TANG Wensong(Department of Otolaryngology Head and Neck Surgery,Chengdu Second People's Hospital,Chengdu,Sichuan 610021)

机构地区：[1]四川省成都市第二人民医院耳鼻咽喉头颈外科,四川成都610021

出　　处：《河北中医》2025年第4期590-594,共5页Hebei Journal of Traditional Chinese Medicine

基　　金：成都市卫生健康委员会2020年成都市医学科研课题(编号:2020003)。

摘　　要：目的探讨迷迭香酸(RA)调节Toll样受体4(TLR4)/核因子-κB(NF-κB)信号通路对急性中耳炎(AOM)大鼠炎症反应的影响。方法通过注射内毒素建立AOM大鼠模型,造模后随机分为AOM组、RA低剂量组(RA-L,5 mg/kg RA)、RA中剂量组(RA-M,10 mg/kg RA)、RA高剂量组(RA-H,20 mg/kg RA)及RA-H+激活剂组(20 mg/kg RA+0.4 mg/kg脂多糖),并以正常大鼠作为对照组。干预结束后,收集大鼠血清,检测血清中肿瘤坏死因子α(TNF-α)、干扰素-γ(IFN-γ)、白细胞介素6(IL-6)水平变化;收集大鼠右侧中耳组织,检测其病理学变化、鼓室黏膜厚度、TNF-α、IFN-γ、IL-6 mRNA表达及TLR4/NF-κB通路相关蛋白表达。结果与对照组相比,AOM组细胞肿胀,并有大量炎性细胞浸润,鼓室黏膜厚度、血清中TNF-α、IFN-γ、IL-6水平及组织中TNF-α、IFN-γ、IL-6 mRNA、TLR4、MyD88、p-NF-κB p65/NF-κB p65表达显著增加(P<0.05);与AOM组相比,RA-L组、RA-M组、RA-H组病理损伤得到缓解,鼓室黏膜厚度、血清中TNF-α、IFN-γ、IL-6水平及组织中TNF-α、IFN-γ、IL-6 mRNA、TLR4、MyD88、p-NF-κB p65/NF-κB p65表达显著降低,组间比较均有统计学差异(P<0.05);与RA-H组相比,RA-H+激活剂组炎性浸润增加,鼓室黏膜厚度、血清中TNF-α、IFN-γ、IL-6水平及组织中TNF-α、IFN-γ、IL-6 mRNA、TLR4、MyD88、p-NF-κB p65/NF-κB p65表达显著增加(P<0.05)。结论RA可抑制AOM大鼠炎症反应,与抑制TLR4/NF-κB信号通路有关。Objective To investigate the impact of rosmarinic acid(RA)on inflammatory response in rats with acute otitis media(AOM)by regulating Toll-like receptor 4(TLR4)/nuclear factor-kappaB(NF-κB)signaling pathway.Methods The AOM models were established by injection of endotoxin in rat.After modeling,they were randomly divided into AOM group,RA low(RA-L,5 mg/kg RA),medium(RA-M,10 mg/kg RA),high dose groups(RA-H,20 mg/kg RA),and RA-H+activator group(20 mg/kg RA+0.4 mg/kg lipopolysaccharide),in addition,normal rats as the blank group(control group).The serum tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),and interleukin-6(IL-6)were detected,and the pathological changes and tympanic mucosa thickness of right middle ear mucosa were assessed.Quantitative real-time polymerase chain reaction(QRT-PCR)was conducted to detect the expression of TNF-α,IFN-γand IL-6 mRNA in mucosa.Western blot was employed to analyze the protein expression of TLR4/NF-κB signaling pathway.Results Compared with the control group,The AOM group had swelling cells,with large number of inflammatory cells infiltrating.Significantly increased tympanic mucosa thickness,the levels of serum TNF-α,IFN-γ,and IL-6,and the expressions of TNF-α,IFN-γ,IL-6 mRNA,TLR4,MyD88,and p-NF-κB p65/NF-κB p65 in tissues were found in the AOM group(P<0.05).Compared with the AOM group,the RA groups presented alleviated pathological damage.The tympanic mucosa thickness,the levels of serum TNF-α,IFN-γ,and IL-6,and the expressions of TNF-α,IFN-γ,IL-6 mRNA,TLR4,MyD88,and p-NF-κB p65/NF-κB p65 in tissues were compared between the AOM group and the RA groups(P<0.05).Compared with the RA-H group,the RA-H+activator group showed increased inflammatory infiltration.Significantly increased tympanic mucosa thickness,the levels of serum TNF-α,IFN-γ,and IL-6,and the expression of TNF-α,IFN-γ,IL-6 mRNAs,TLR4,MyD88,p-NF-κB p65/NF-κB p65 in tissues were detected in the RA-H+activator group(P<0.05).Conclusion RA can inhibit the inflammatory response of AOM rats by regu

关 键 词：中耳炎 迷迭香酸 动物实验 大鼠 炎症反应 

分 类 号：R764.21[医药卫生—耳鼻咽喉科]