| 努尔阿米娜·铁力瓦尔迪,关 景,李晶晶,李 新,韩利梅.胃饥饿素对哮喘大鼠气道组织损伤、血清Th1/Th2细胞因子以及TLR4/NF-κB信号通路的影响[J].,2024,(10):1833-1837 |
| 胃饥饿素对哮喘大鼠气道组织损伤、血清Th1/Th2细胞因子以及TLR4/NF-κB信号通路的影响 |
| The Influences of Airway Tissue Injury, Serum Th1/Th2 Cytokines and TLR4/NF-κB Signal Pathway by Ghrelin in Asthma Rats |
| 投稿时间：2023-11-07 修订日期：2023-11-30 |
| DOI：10.13241/j.cnki.pmb.2024.10.006 |
| 中文关键词: 胃饥饿素 哮喘 Toll样受体4 核转录因子-κB 气道损伤 Th1/Th2细胞因子 |
| 英文关键词: Ghrelin Asthma Toll like receptor 4 Nuclear transcription factor- κB Airway injury Th1/Th2 cytokines |
| 基金项目:新疆维吾尔自治区自然科学基金项目（2021D01C269） |
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| 中文摘要: |
| 摘要 目的：探讨胃饥饿素介导Toll样受体4（TLR4）/核转录因子-κB（NF-κB）信号通路对哮喘模型大鼠的气道组织损伤和血清Th1/Th2细胞因子的影响机制。方法：选择健康Wistar雄性大鼠平均7周龄（体重平均220 g）共40只，随机分为4组，每组10只，分别为对照组、模型组、胃饥饿素低浓度组（1 μmol/L）和高浓度组（5 μmol/L）。除了对照组，其他三组复制急性哮喘模型，胃饥饿素低浓度组和高浓度组腹腔注射10 mL/kg胃饥饿素，对照组和模型组注射等量生理盐水。造模结束24 h 后评估各组大鼠的哮喘症状评分，检测血清中性粒细胞与淋巴细胞百分比，计算中性粒细胞与淋巴细胞比值（NLR），ELISA法检测血清IgE、Th1型细胞因子IFN-γ和Th2 型细胞因子 IL-4，计算IFN-γ/IL-4，HE染色肺组织计算气道壁厚度和气管平滑肌厚度，评估气道损伤程度，Western blot法检测肺组织TLR4和NF-κB p65蛋白相对表达量。结果：与对照组相比，模型组大鼠哮喘症状评分、淋巴细胞百分比、IgE、IL-4、气道壁厚度和气管平滑肌厚度、TLR4和NF-κB p65蛋白相对表达量均显著增加，而NLR、IFN-γ和IFN-γ/IL-4显著降低（P＜0.05）。与模型组相比，胃饥饿素低浓度组和高浓度组大鼠哮喘症状评分、淋巴细胞百分比、IgE、IL-4、气道壁厚度和气管平滑肌厚度、TLR4和NF-κB p65蛋白相对表达量明显降低，而NLR、IFN-γ和IFN-γ/IL-4明显升高（P＜0.05）。与低浓度组相比，高浓度组上述指标也存在显著差异（P＜0.05）。结论：胃饥饿素可能通过抑制TLR4/ NF-κB信号通路活性，进而改善哮喘症状，降低炎症反应，调节Th1/Th2平衡，减轻气道组织损伤，且表现出一定的浓度依赖性。胃饥饿素有望成为临床干预哮喘的新途径。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the mechanism of Ghrelin on airway tissue injury and serum Th1/Th2 cytokines in asthma model rats via Toll like receptor 4 (TLR4)/nuclear transcription factors-κB (NF-κB) signal pathway. Methods: A total of 40 healthy Wistar male rats with average age of 7 weeks (average weight of 220 g) were randomly divided into 4 groups, with 10 rats in each group, they were control group, model group, low concentration group of Ghrelin (1 μmol/L) and high concentration group (5 μmol/L). In addition to the control group, the other three groups replicated acute asthma models. The low concentration and high concentration groups of Ghrelin were intraperitoneally injected with 10 mL/kg, while the control group and model group were injected with equal amount of physiological saline. After 24 hours of modeling, asthma symptom score of each group rats were evaluated, the percentages serum neutrophils and lymphocytes were measured, then neutrophils to lymphocytes ratio (NLR) was calculated, serum IgE, Th1 cytokine IFN and Th2 cytokine IL-4 were detected by ELISA method, then IFN-γ/ IL-4 was calculated, lung tissue was stained with HE to calculate airway wall thickness and tracheal smooth muscle thickness, for airway injury degree was evaluated, Western blot method was to detect TLR4 and NF-κB p65 proteins relative expression in lung tissue. Results: Compared with the control group, the asthma symptom score, lymphocyte percentage, IgE, IL-4, airway wall thickness and tracheal smooth muscle thickness, TLR4 and NF-κB p65 protein relative expression levels in the model group rats were significantly higher, while NLR, IFN-γ and IFN-γ/IL-4 were significantly lower(P<0.05). Compared with the model group, the asthma symptom score, lymphocyte percentage, IgE, IL-4, airway wall thickness, tracheal smooth muscle thickness, TLR4, and NF-κB p65 protein relative expression levels in the low and high concentration groups of Ghrelin were significantly less, while NLR, IFN-γ and IFN-γ/IL-4 were significantly more(P<0.05). Compared with the low concentration group, above indicators in the high concentration group were also significantly differen(P<0.05). Conclusion: Ghrelin may inhibit TLR4/NF- κB signal pathway activity to improve asthma symptom, reduce inflammatory, regulate Th1/Th2 balance, alleviate airway tissue injury, and exhibit a certain concentration dependence. Ghrelin is expected to become a new pathway for clinical intervention in asthma. |
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