厄多司坦通过调节 TLR4 信号通路对大鼠中耳积液的影响。
Effect of Erdosteine on Middle Ear Effusion in Rats by Mediating TLR4 Signaling Pathway.
机构信息
Department of Otolaryngology Head and Neck Surgery, The Third Affiliated Hospital, Army Military Medical University, Chongqing 400042, China.
出版信息
Biomed Res Int. 2021 Oct 25;2021:9968907. doi: 10.1155/2021/9968907. eCollection 2021.
The study aimed to investigate the effect of erdosteine on middle ear effusion in rats through mediating the Toll-like receptor 4 (TLR4) signaling pathway. Rats were injected with endotoxin to prepare the model of acute secretory otitis media (SOM). Then, they were divided into an acute SOM model group (model group, = 15) and erdosteine treatment group (18 mg/kg, gavage, treatment group, = 15). Besides, a normal group ( = 15) was set up. Two weeks later, routine biochemical indicators such as aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were detected. The inflammatory effusion due to otitis media was scored. The content of myeloperoxidase (MPO), matrix metalloproteinase (MMP), and tumor necrosis factor-beta (TNF-) in middle ear lavage fluid was detected via enzyme-linked immunosorbent assay (ELISA). Additionally, histomorphological changes were observed with the help of hematoxylin-eosin (HE) staining, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assays were carried out to measure the expression levels of TLR4 pathway genes and proteins as well as the messenger ribonucleic acid (mRNA) expression levels of key factors for otitis media (mucin 2 (MUC2) and MUC5A). In the model group, the levels of AST, ALP, and glutamic-pyruvic transaminase (GPT) were significantly increased ( < 0.05). Besides, the content of MPO, MMP, and TNF- was overtly raised in the model group ( < 0.05), while it was notably lowered in the treatment group ( < 0.05). In the treatment group, the cilia were slightly swollen, and inflammatory cells were fewer. The mRNA levels of MUC2, MUC5A, and pathway genes TLR4 and c-Jun N-terminal kinase (JNK) were elevated in the model group. In addition, the protein assay results revealed that the protein levels of TLR4 and JNK were evidently increased in the model group. Erdosteine can treat the middle ear effusion in rats by repressing the activation of the TLR4 signaling pathway.
本研究旨在通过调节 Toll 样受体 4（TLR4）信号通路，探讨厄多司坦对大鼠中耳积液的影响。通过向大鼠注射内毒素制备急性分泌性中耳炎（SOM）模型。然后，将其分为急性 SOM 模型组（模型组，n=15）和厄多司坦治疗组（18mg/kg，灌胃，治疗组，n=15）。此外，还设立了正常组（n=15）。2 周后，检测天冬氨酸转氨酶（AST）和碱性磷酸酶（ALP）等常规生化指标。对中耳炎炎症性渗出进行评分。采用酶联免疫吸附试验（ELISA）检测中耳灌洗液中髓过氧化物酶（MPO）、基质金属蛋白酶（MMP）和肿瘤坏死因子-β（TNF-）的含量。此外，通过苏木精-伊红（HE）染色观察组织形态学变化，采用定量逆转录-聚合酶链反应（qRT-PCR）和 Western blot 检测 TLR4 通路基因和蛋白以及中耳炎关键因子（粘蛋白 2（MUC2）和 MUC5A）的信使核糖核酸（mRNA）表达水平。在模型组中，AST、ALP 和谷丙转氨酶（GPT）水平明显升高（<0.05）。此外，模型组 MPO、MMP 和 TNF-含量明显升高（<0.05），而治疗组明显降低（<0.05）。在治疗组中，纤毛轻度肿胀，炎症细胞减少。模型组 MUC2、MUC5A、通路基因 TLR4 和 c-Jun N-末端激酶（JNK）的 mRNA 水平升高。此外，蛋白检测结果表明，模型组 TLR4 和 JNK 蛋白水平明显升高。厄多司坦通过抑制 TLR4 信号通路的激活来治疗大鼠中耳积液。
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