乌本苷可调节高Th2型哮喘小鼠的气道重塑
2022/06/17
摘要
背景：乌本苷是Na+/K+-ATP酶的抑制剂，是肾上腺皮质和下丘脑合成的一种内源性激素。此前的研究发现，瓦巴因能有效抑制2型炎症等急性炎症反应，并调节免疫过程。
目的：本研究旨在探讨乌本苷对过敏性哮喘的影响。
方法：采用卵清蛋白(OVA)诱导BALB/c小鼠慢性气道过敏性炎症。这些动物接受了乌本苷或标准药物布地奈德的治疗。评估了以下参数:细胞迁移、细胞因子谱、IgE水平、肺组织改变和MAPK激活。
结果：首先，通过支气管肺泡灌洗液(BALF)细胞计数和肺组织学分析(HE染色)观察到，乌本苷减少了OVA诱导的细胞向肺的迁移。此外，乌本苷负向调节警报素(IL-33和TSLP)，高Th2细胞因子水平(IL-13和IL-4)和组织重塑标志物，如TNF-α和TGF-13。与OVA组相比，使用乌本苷治疗也分别降低了BALF和血清中OVA特异性IgE的滴度。OVA诱导的肺组织学参数，包括胶原沉积和粘液产生也被乌本苷治疗减弱。最后，我们的结果表明，在该模型中，乌本苷可抑制p38丝裂原活化蛋白激酶(MAPK)信号通路。作为一种甾体抗炎标准药物，布地奈德可降低所有这些参数。
结论:这些数据表明，乌本苷除了急性抗炎作用，还能调节过敏性哮喘。
Ouabain modulates airway remodeling caused by Th2-high asthma in mice
Galvao JGFM, Cavalcante-Silva LHA, Lima ED, et al.
Abstract
BACKGRUND:Ouabain, an inhibitor of Na+/K+-ATPase, is a type of endogenous hormone synthesized in the adrenal cortex and hypothalamus. Previous studies found that ouabain potently inhibited acute inflammatory reactions such as type 2 inflammation and regulated immunological processes.
OBJECTIVE:In this study, we aimed to investigate ouabain effect on allergic asthma.
METHODS:BALB/c mice were submitted to chronic airway allergic inflammation induced by an ovalbumin (OVA) protocol. The animals were treated with ouabain or standard drug, budesonide. The following parameters were evaluated: cell migration, cytokine profile, IgE levels, lung histological modifications and MAPK activation.
RESULTS:At first, it was observed that ouabain reduced OVA-induced cell migration into the lung, observed by bronchoalveolar lavage fluid (BALF) cell counting and lung histological analysis (HE stain). Additionally, ouabain negatively modulated alarmins (IL-33 and TSLP), Th2 high cytokines levels (IL-13 and IL-4) and tissue remodeling markers such as TNF-alpha and TGF-13,Treatment with ouabain also reduced OVA-specific IgE titers in BALF and serum, respectively, when compared to the OVA group. Lung histological parameters, including collagen deposition and mucus production induced by OVA were also attenuated by ouabain treatment. Finally, our results showed that p38 mitogen-activated protein kinase (MAPK) signaling pathways were suppressed by ouabain in this model. All these parameters were reduced by budesonide, a steroidal anti-inflammatory standard drug.
CONCLUSIONS: These data together suggest that, in addition to its acute anti-inflammatory action, ouabain is also able to modulate allergic asthma.
背景：乌本苷是Na+/K+-ATP酶的抑制剂，是肾上腺皮质和下丘脑合成的一种内源性激素。此前的研究发现，瓦巴因能有效抑制2型炎症等急性炎症反应，并调节免疫过程。
目的：本研究旨在探讨乌本苷对过敏性哮喘的影响。
方法：采用卵清蛋白(OVA)诱导BALB/c小鼠慢性气道过敏性炎症。这些动物接受了乌本苷或标准药物布地奈德的治疗。评估了以下参数:细胞迁移、细胞因子谱、IgE水平、肺组织改变和MAPK激活。
结果：首先，通过支气管肺泡灌洗液(BALF)细胞计数和肺组织学分析(HE染色)观察到，乌本苷减少了OVA诱导的细胞向肺的迁移。此外，乌本苷负向调节警报素(IL-33和TSLP)，高Th2细胞因子水平(IL-13和IL-4)和组织重塑标志物，如TNF-α和TGF-13。与OVA组相比，使用乌本苷治疗也分别降低了BALF和血清中OVA特异性IgE的滴度。OVA诱导的肺组织学参数，包括胶原沉积和粘液产生也被乌本苷治疗减弱。最后，我们的结果表明，在该模型中，乌本苷可抑制p38丝裂原活化蛋白激酶(MAPK)信号通路。作为一种甾体抗炎标准药物，布地奈德可降低所有这些参数。
结论:这些数据表明，乌本苷除了急性抗炎作用，还能调节过敏性哮喘。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（International Immunopharmacology, 2022, 109. doi:10.1016/j.intimp.2022.108808）
（International Immunopharmacology, 2022, 109. doi:10.1016/j.intimp.2022.108808）
Ouabain modulates airway remodeling caused by Th2-high asthma in mice
Galvao JGFM, Cavalcante-Silva LHA, Lima ED, et al.
Abstract
BACKGRUND:Ouabain, an inhibitor of Na+/K+-ATPase, is a type of endogenous hormone synthesized in the adrenal cortex and hypothalamus. Previous studies found that ouabain potently inhibited acute inflammatory reactions such as type 2 inflammation and regulated immunological processes.
OBJECTIVE:In this study, we aimed to investigate ouabain effect on allergic asthma.
METHODS:BALB/c mice were submitted to chronic airway allergic inflammation induced by an ovalbumin (OVA) protocol. The animals were treated with ouabain or standard drug, budesonide. The following parameters were evaluated: cell migration, cytokine profile, IgE levels, lung histological modifications and MAPK activation.
RESULTS:At first, it was observed that ouabain reduced OVA-induced cell migration into the lung, observed by bronchoalveolar lavage fluid (BALF) cell counting and lung histological analysis (HE stain). Additionally, ouabain negatively modulated alarmins (IL-33 and TSLP), Th2 high cytokines levels (IL-13 and IL-4) and tissue remodeling markers such as TNF-alpha and TGF-13,Treatment with ouabain also reduced OVA-specific IgE titers in BALF and serum, respectively, when compared to the OVA group. Lung histological parameters, including collagen deposition and mucus production induced by OVA were also attenuated by ouabain treatment. Finally, our results showed that p38 mitogen-activated protein kinase (MAPK) signaling pathways were suppressed by ouabain in this model. All these parameters were reduced by budesonide, a steroidal anti-inflammatory standard drug.
CONCLUSIONS: These data together suggest that, in addition to its acute anti-inflammatory action, ouabain is also able to modulate allergic asthma.
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低T2重症哮喘人群的病情加重情况和危险因素
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大鼠肺和鼻上皮的过敏性炎症受组织特异性miRNA表达的调控
