藻蓝蛋白在脂多糖和海水诱导的急性肺损伤中的治疗效果及可能机制。
The Therapeutic Effect and the Possible Mechanism of C-Phycocyanin in Lipopolysaccharide and Seawater-Induced Acute Lung Injury.
机构信息
Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan, 316022, People's Republic of China.
Zhoushan Institute of Calibration and Testing for Quality and Technical Supervision, Zhoushan, 316012, Zhejiang, People's Republic of China.
出版信息
Drug Des Devel Ther. 2022 Apr 6;16:1025-1040. doi: 10.2147/DDDT.S347772. eCollection 2022.
BACKGROUND
Seawater drowning-induced acute lung injury (ALI) is a severe clinical condition characterized by increased alveolar-capillary permeability, excessive inflammatory response, and refractory hypoxemia. C-phycocyanin (C-PC), a biliprotein found in blue-green algae such as spirulina platensis, is widely used in the food and dietary nutritional supplement fields due to its beneficial pharmacological effects. Previous studies have revealed that C-PC has anti-inflammatory, antioxidant, and anti-apoptotic activities.
PURPOSE
Therefore, this study investigated the protective effect and underlying mechanisms of C-PC on lipopolysaccharide (LPS) and seawater (SW) induced ALI (SW and LPS-induced ALI).
METHODS
An SW and LPS mouse model of ALI mice was established through intratracheal administration of 5mg/kg LPS and 25% SW. Different doses of C-PC (100, 200 and 400 mg/kg) were administered by intraperitoneal injection for seven days. In addition, gap junction communication in RAW264.7 and MLE-12 cells was determined following stimulation with 25% SW and 10 μg/ml LPS after treatment with C-PC (120 μg/ml). Moreover, the arterial partial pressure of oxygen, lung wet/dry weight ratios, total protein content and MPO levels in the bronchoalveolar lavage fluid (BALF), and the histopathologic and ultrastructure staining of the lung tissues were determined. The oxidative stress index, levels of the pro-inflammatory mediators, epithelial cell viability and apoptosis, and the regulatory effect of C-PC on the NF-κB/NLRP3 axis were investigated.
RESULTS
The results showed that C-PC significantly alleviated pathological damages, suppressed oxidative stress, inflammation and apoptosis, and enhanced the viability of epithelial cells in the lung tissues. Furthermore, C-PC was shown to inhibit activation of the NF-κB/NLRP3 pathway and the formation of the NLRP3 inflammasome complex.
CONCLUSIONS
In conclusion, C-PC shows promising therapeutic value in SW and LPS-induced ALI/ARDS, providing new insight into ALI/ARDS treatment.
背景
海水溺水导致的急性肺损伤（ALI）是一种严重的临床病症，其特征为肺泡毛细血管通透性增加、过度炎症反应和难治性低氧血症。C-藻蓝蛋白（C-PC）是一种蓝藻中的二肽，如螺旋藻中发现的蓝藻蛋白，由于其有益的药理作用，被广泛应用于食品和膳食营养补充剂领域。先前的研究表明，C-PC 具有抗炎、抗氧化和抗细胞凋亡作用。
目的
因此，本研究旨在探讨 C-PC 对脂多糖（LPS）和海水（SW）诱导的 ALI（SW 和 LPS 诱导的 ALI）的保护作用及其潜在机制。
方法
通过气管内给予 5mg/kg LPS 和 25% SW 建立 SW 和 LPS 诱导的 ALI 小鼠模型。通过腹腔注射不同剂量的 C-PC（100、200 和 400mg/kg）进行 7 天治疗。此外，在用 25% SW 和 10μg/ml LPS 刺激后，用 C-PC（120μg/ml）处理 RAW264.7 和 MLE-12 细胞，测定缝隙连接通讯。还测定了动脉血氧分压、肺湿/干重比、支气管肺泡灌洗液（BALF）中的总蛋白含量和 MPO 水平，以及肺组织的组织病理学和超微结构染色。研究了 C-PC 对 NF-κB/NLRP3 轴的调节作用以及氧化应激指标、促炎介质水平、上皮细胞活力和凋亡的影响。
结果
结果表明，C-PC 可显著减轻病理损伤，抑制氧化应激、炎症和细胞凋亡，提高肺组织上皮细胞活力。此外，C-PC 可抑制 NF-κB/NLRP3 通路的激活和 NLRP3 炎性小体复合物的形成。
结论
总之，C-PC 在 SW 和 LPS 诱导的 ALI/ARDS 中具有有前景的治疗价值，为 ALI/ARDS 的治疗提供了新的思路。
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