黄芪皂苷Ⅱ对哮喘幼年大鼠 IL-21 / STAT3 通路及气道炎症反应的影响
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1.齐齐哈尔市第一医院新生儿科,黑龙江 齐齐哈尔 161000; 2.哈尔滨市道里区人民医院儿科,哈尔滨 150000

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R-33

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Effects of astragaloside II on the IL-21 / STAT3 pathway and airway inflammation in young asthmatic rats
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1.Department of Neonatology, the First Hospital of Qiqihar, Qiqihar 161000, China. 2. Department of Pediatrics, Daoli District People’s Hospital Harbin City, Harbin 150000

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    摘要:

    目的 探究黄芪皂苷Ⅱ对哮喘幼年大鼠白细胞介素-21 ( IL-21) / 信号转导和转录活化因子 3 (STAT3)通路及气道炎症反应的影响。 方法 将幼年大鼠随机分成对照组、模型组、黄芪皂苷Ⅱ低、中、高剂量组和地塞米松组,每组 12 只,除对照组外,其余各组采用卵清蛋白(OVA)激发制备幼年大鼠哮喘模型,各组幼年大鼠分别给予相应药物治疗,检测气道反应性(Penh 值),采用酶联免疫吸附试验(ELISA) 法检测血清和肺泡灌洗液 (BALF)上清液中白细胞介素-6( IL-6)、白细胞介素-21( IL-21)、转化生长因子-β1( TGF-β1) 含量;苏木素-伊红 (HE)染色观察幼年大鼠肺组织病理变化;蛋白免疫印迹(Western blot)法检测幼年大鼠肺组织中 IL-21、磷酸化- STAT3(p-STAT3)、STAT3 蛋白表达情况。 结果 与对照组相比,模型组幼年大鼠可见肺组织中支气管上皮结构紊乱,上皮细胞水肿脱落,炎性细胞浸润等病变,不同浓度乙酰胆碱(Ach)激发后 Penh 值、BALF 中白细胞总数、嗜酸性粒细胞、中性粒细胞、淋巴细胞和巨噬细胞数、BALF 上清液和血清中 IL-6、IL-21 和 TGF-β1 含量、肺组织炎症评分、肺组织中 IL-21、p-STAT3 蛋白表达显著升高(P<0. 05)。与模型组相比,黄芪皂苷Ⅱ各处理组和地塞米松组幼年大鼠肺组织结构逐渐完整,不同浓度 Ach 激发后 Penh 值、BALF 中白细胞总数、嗜酸性粒细胞、中性粒细胞、淋巴细胞和巨噬细胞数、BALF 上清液和血清中 IL-6、IL-21 和 TGF-β1 含量、肺组织炎症评分、肺组织中 IL-21、p-STAT3 蛋白表达显著降低(P<0. 05)。 且随着黄芪皂苷Ⅱ剂量的增加,幼年大鼠不同浓度 Ach 激发后 Penh 值、BALF 中白细胞总数、嗜酸性粒细胞、中性粒细胞、淋巴细胞和巨噬细胞数、BALF 上清液和血清中 IL-6、IL-21 和 TGF-β1 含量、 肺组织炎症评分、肺组织中 IL-21、p-STAT3 蛋白表达依次降低(P<0. 05)。 结论 黄芪皂苷Ⅱ可能通过抑制 IL-21 / STAT3 通路,减轻哮喘幼年大鼠气道炎症反应,修复肺组织结构,改善哮喘症状。

    Abstract:

    Objective To investigate the effects of astragaloside II on the interleukin (IL)-21 / signal transducer and activator of transcription 3 (STAT3) pathway and airway inflammation in young asthmatic rats. Methods Young rats were randomly divided into control, model, astragaloside II low-dose, astragaloside II medium-dose, astragaloside II high- dose, and dexamethasone groups with 12 rats in each group. Except for the control group, the groups were challenged with ovalbumin to prepare asthma models and the rats in each group were treated with corresponding drugs. Airway reactivity (Penh value) was measured and the levels of IL-6, IL-21, and transforming growth factoR-β1 (TGF-β1) in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assays. HE staining was used to observe pathological changes in lung tissues. Western blot was used to detect protein expression of IL-21, phosphorylated STAT3 (p-STAT3), and STAT3 in lung tissues of the rats. Results Compared with the control group, the structure of bronchial epithelial tissue was disordered, pulmonary epithelial cells were edematous and exfoliated, and inflammatory cells had infiltrated in the model group. After stimulation with acetylcholine (Ach) at various concentrations, the Penh value, total number of leukocytes, numbers of eosinophils, neutrophils, lymphocytes, and macrophages in BALF, the contents of IL-6, IL-21, and TGF-β1 in BALF and serum, the lung tissue inflammation score, and protein expression of IL-21 and p- STAT3 in lung tissues were increased significantly (P< 0.05). Compared with the model group, the lung tissue structure of young rats in astragaloside II treatment groups and dexamethasone group was gradually complete, after stimulation with Ach at various concentrations, the Penh value, total number of leukocytes, numbers of eosinophils, neutrophils, lymphocytes, and macrophages in BALF, contents of IL-6, IL-21, and TGF-β1 in BALF and serum, the lung tissue inflammation score, and protein expression of IL-21 and p-STAT3 in lung tissues were decreased significantly (P< 0.05), which were dependent on the dose. Conclusions Astragaloside II alleviates airway inflammation in young asthmatic rats, repairs lung tissue and the bronchial structure, and improves asthmatic symptoms by inhibiting the IL-21 / STAT3 pathway.

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伍 爽,李 微,黎 达,辛 迪,陈晓凤,李 雪.黄芪皂苷Ⅱ对哮喘幼年大鼠 IL-21 / STAT3 通路及气道炎症反应的影响[J].中国比较医学杂志,2021,31(12):53~59.

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  • 收稿日期:2020-10-21
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  • 在线发布日期: 2022-01-28
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