PDF(Pubmed)
Abstract：
Acute lung injury (ALI) represents a life-threatening condition with high morbidity and mortality despite modern mechanical ventilators and multiple pharmacological strategies. Therefore, there is a need to develop efficacious interventions with minimal side effects. The anti-inflammatory activities of sea cucumber (Cucumaria frondosa) and wild blueberry (Vaccinium angustifolium) extracts have been reported recently. However, their anti-inflammatory activities and the mechanism of action against ALI are not fully elucidated. Thus, the present study aims to understand the mechanism of the anti-inflammatory activity of sea cucumber and wild blueberry extracts in the context of ALI. Experimental ALI was induced via intranasal lipopolysaccharide (LPS) instillation in C57BL/6 mice and the anti-inflammatory properties were determined by cytokine analysis, histological examination, western blot, and qRT-PCR. The results showed that oral supplementation of sea cucumber extracts repressed nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thereby downregulating the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) in the lung tissue and in the plasma. Wild blueberry extracts also suppressed the expression of IL-4. Furthermore, the combination of sea cucumber and wild blueberry extracts restrained MAPK signaling pathways by prominent attenuation of phosphorylation of NF-κB, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) while the levels of pro-inflammatory cytokines were significantly suppressed. Moreover, there was a significant and synergistic reduction in varying degrees of ALI lesions such as distorted parenchyma, increased alveoli thickness, lymphocyte and neutrophil infiltrations, fibrin deposition, pulmonary emphysema, pneumonia, intra-alveolar hemorrhage, and edema. The anti-inflammatory effect of the combination of sea cucumber and wild blueberry extracts is associated with suppressing MAPK and NF-κB signaling pathways, thereby significantly reducing cytokine storm in LPS-induced experimental ALI.
摘要：
尽管采用了现代机械呼吸机和多种药理策略，但急性肺损伤（ALI）仍是一种危及生命的疾病，具有很高的发病率和死亡率。因此,需要开发副作用最小的有效干预措施.最近已经报道了海参（Cucumariafrondosa）和野生蓝莓（Vacciniumangustifolium）提取物的抗炎活性。然而,它们的抗炎活性和抗ALI的作用机制尚未完全阐明。因此，本研究旨在了解海参和野生蓝莓提取物在ALI中的抗炎作用机制。通过对C57BL/6小鼠鼻内滴入脂多糖（LPS）诱导实验性ALI，并通过细胞因子分析确定抗炎特性，组织学检查,westernblot,和qRT-PCR。结果表明,口服海参提取物抑制核因子κB(NF-κB)和丝裂原活化蛋白激酶(MAPK)信号通路,从而下调白细胞介素（IL）-1β的表达，肺组织和血浆中的IL-6和肿瘤坏死因子（TNF）。野生蓝莓提取物也抑制IL-4的表达。此外，海参和野生蓝莓提取物的组合通过显著减弱NF-κB的磷酸化来抑制MAPK信号通路,c-Jun氨基末端激酶（JNK），和细胞外信号调节激酶（ERK），而促炎细胞因子的水平显着受到抑制。此外，不同程度的ALI病变，如实质扭曲，肺泡厚度增加，淋巴细胞和中性粒细胞浸润，纤维蛋白沉积，肺气肿,肺炎,肺泡内出血,和水肿。海参和野生蓝莓提取物的联合抗炎作用与抑制MAPK和NF-κB信号通路有关，从而显著减少LPS诱导的实验性ALI中的细胞因子风暴。
