6-Gingerol attenuates sepsis-induced acute lung injury by suppressing NLRP3 inflammasome through Nrf2 activation.

IF 1.7 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Folia histochemica et cytobiologica Pub Date : 2023-01-01 DOI:10.5603/FHC.a2023.0002

Quanli Pan, Peng Liu, Min Wan

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Abstract

Introduction: Sepsis is characterized by an overactive inflammatory response. Acute lung injury (ALI) is the most common type of organ injury in sepsis, with high morbidity and mortality. 6-Gingerol is the main bioactive compound of ginger, and it possesses anti-inflammatory bioactivity in different diseases. This study is aimed to explore the specific function of 6-Gingerol in sepsis-induced ALI.

Material and methods: Lipopolysaccharide (LPS) was intraperitoneally injected into Sprague-Dawley rats for establishing the ALI models in vivo. The ALI rats were intraperitoneally injected with 20 mg/kg 6-Gingerol. The contents of oxidative stress markers malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were detected in the lung tissues of ALI rats. The concentrations of inflammatory factors [Tumor Necrosis Factor alpha (TNF-α), interleukin (IL)-6, and IL-1β] were measured by ELISA. Inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) of rats was tested. Western blot was utilized to test the protein levels of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in lung tissues. Furthermore, immunohistochemical staining was applied for testing the expression of NLRP3 inflammasome in lung tissues.

Results: The pathological changes in ALI rats were characterized by increased accumulation of inflammatory cells, alveolar hemorrhage, and pulmonary interstitial edema. However, the degree of pathological injury of lung tissues was significantly improved after 6-Gingerol treatment. Additionally, 6-Gingerol significantly attenuated the lung wet/dry ratio and protein permeability index (PPI) of LPS-induced rats. Furthermore, 6-Gingerol repressed oxidative stress and inflammatory reaction in LPS-induced rats by reducing the contents of MDA, GSH, SOD, TNF-α, IL-6, and IL-1β in the lung. LPS-induced infiltration of eosinophils, macrophages, neutrophils, and lymphocytes into lung was suppressed by 6-Gingerol administration. Moreover, 6-Gingerol activated Nrf2/HO-1 signaling and repressed LPS-induced‑NLRP3 inflammasome expression in lung tissues of LPS-induced rats. Intraperitoneal injection of ML385 (Nrf2 inhibitor) treatment into rats reversed the effects of 6-Gingerol on lung injury, inflammation, and oxidative stress in LPS-subjected rats.

Conclusions: 6-Gingerol attenuates sepsis-induced ALI by suppressing NLRP3 inflammasome activation via stimulation of Nrf2.

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6-姜辣素通过Nrf2激活抑制NLRP3炎性体，减轻败血症诱导的急性肺损伤。

败血症的特点是炎症反应过度活跃。急性肺损伤(ALI)是脓毒症中最常见的器官损伤类型，具有很高的发病率和死亡率。6-姜辣素是生姜的主要生物活性成分，对多种疾病均具有抗炎生物活性。本研究旨在探讨6-姜辣素在脓毒症诱导ALI中的具体作用。材料与方法:将脂多糖(LPS)腹腔注射到Sprague-Dawley大鼠体内，建立ALI模型。大鼠腹腔注射6-姜辣素20 mg/kg。检测ALI大鼠肺组织中氧化应激标志物丙二醛(MDA)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)的含量。采用ELISA法检测炎症因子[肿瘤坏死因子α (TNF-α)、白细胞介素(IL)-6、IL-1β]的浓度。观察了大鼠支气管肺泡灌洗液(BALF)中炎症细胞的浸润情况。Western blot检测大鼠肺组织核因子-红系2相关因子(Nrf2)和血红素加氧酶-1 (HO-1)蛋白水平。采用免疫组化染色法检测NLRP3炎性体在肺组织中的表达。结果:ALI大鼠的病理变化表现为炎症细胞积聚增加、肺泡出血、肺间质水肿。但6-姜辣素治疗后肺组织病理损伤程度明显改善。6-姜辣素显著降低lps诱导大鼠肺湿/干比和蛋白通透指数(PPI)。6-姜辣素通过降低肺组织中MDA、GSH、SOD、TNF-α、IL-6和IL-1β的含量，抑制lps诱导大鼠的氧化应激和炎症反应。6-姜辣素可抑制lps诱导的嗜酸性粒细胞、巨噬细胞、中性粒细胞和淋巴细胞向肺的浸润。此外，6-姜辣素激活Nrf2/HO-1信号，抑制lps诱导的大鼠肺组织中NLRP3炎症小体的表达。大鼠腹腔注射ML385 (Nrf2抑制剂)治疗逆转了6-姜辣素对lps诱导大鼠肺损伤、炎症和氧化应激的影响。结论:6-姜辣素通过刺激Nrf2抑制NLRP3炎性体的激活，从而减轻败血症诱导的ALI。

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来源期刊

Folia histochemica et cytobiologica 生物-生化与分子生物学

CiteScore

2.80

自引率

6.70%

发文量

审稿时长

6-12 weeks

期刊介绍： "Folia Histochemica et Cytobiologica" is an international, English-language journal publishing articles in the areas of histochemistry, cytochemistry and cell & tissue biology. "Folia Histochemica et Cytobiologica" was established in 1963 under the title: ‘Folia Histochemica et Cytochemica’ by the Polish Histochemical and Cytochemical Society as a journal devoted to the rapidly developing fields of histochemistry and cytochemistry. In 1984, the profile of the journal was broadened to accommodate papers dealing with cell and tissue biology, and the title was accordingly changed to "Folia Histochemica et Cytobiologica". "Folia Histochemica et Cytobiologica" is published quarterly, one volume a year, by the Polish Histochemical and Cytochemical Society.