Previous studies have suggested that pyroptosis may play an important role in LPS-induced acute lung injury (ALI), but the exact mechanism of pyroptosis induction and the role of Angiotensin-converting enzyme 2 (ACE2)/Ang (1–7)/Mas axis in pyroptosis has not been investigated yet. The present study aimed to establish a mice model of ALI and clarify the involvement of pyroptosis and ACE2/Ang (1–7)/Mas axis. The results showed that LPS induced pyroptosis in lung, demonstrated by increased expression of Gasdermin D (GSDMD), cleaved GSDMD, IL-1β, and Caspase-1. Treatment of Ang (1–7) significantly reduced the severity of ALI and pyroptosis, while AngII significantly exaggerated them. Furthermore, ACE2 activator resorcinolnaphthalein (RES) significantly reduced the severity of ALI and pyroptosis, but ACE2 inhibitor MLN-4760 and Mas inhibitor A779 significantly exaggerated them, suggesting that the ACE2/Ang (1–7)/Mas axis was involved in the pyroptosis in LPS-induced ALI. In addition, Ang (1–7) and RES significantly decreased the levels of NLRP3, which were increased by AngII and A779. NLRP3 knockout significantly reduced the severity of ALI and pyroptosis. In conclusion, pyroptosis played an important role in ALI induced by LPS. The ACE2/Ang (1–7)/Mas axis negatively regulated the pyroptosis and protected mice against LPS-induced ALI through NLRP3 inhibition. The present study expanded our understating of the role of ACE2/Ang (1–7)/Mas axis in ALI by providing a novel explanation that it may regulate the pyroptosis in ALI.

先前的研究表明，细胞凋亡可能在LPS诱发的急性肺损伤（ALI）中起重要作用，但是其引起细胞凋亡的确切机制以及血管紧张素转换酶2（ACE2）/ Ang（1-7）/ Mas的作用尚未发现焦磷酸化中的轴。本研究旨在建立ALI小鼠模型并阐明烧伤和ACE2 / Ang（1-7）/ Mas轴的参与。结果表明，LPS诱导的肺部细胞凋亡，由Gasdermin D（GSDMD），GSMDD，IL-1β和Caspase-1的表达增加证明。Ang（1–7）的治疗可显着降低ALI和烧伤的严重程度，而AngII则可将其严重放大。此外，ACE2激活物间苯二酚萘（RES）可以显着降低ALI的严重程度和发烧，但是ACE2抑制剂MLN-4760和Mas抑制剂A779显着夸大了它们，表明ACE2 / Ang（1-7）/ Mas轴参与了LPS诱导的ALI的热解。另外，Ang（1–7）和RES显着降低了NLRP3的水平，而AngII和A779增加了NLRP3的水平。NLRP3基因敲除显着降低了ALI和焦磷酸化的严重程度。总之，细胞凋亡在LPS诱导的ALI中起重要作用。ACE2 / Ang（1-7）/ Mas轴负调控发烧，并通过NLRP3抑制保护小鼠免受LPS诱导的ALI。本研究通过提供新的解释，即它可能调节ALI的凋亡，从而扩大了我们对ACE2 / Ang（1-7）/ Mas轴在ALI中的作用的低估。提示ACE2 / Ang（1-7）/ Mas轴参与了LPS诱导的ALI的热解。另外，Ang（1–7）和RES显着降低了NLRP3的水平，而AngII和A779增加了NLRP3的水平。NLRP3基因敲除显着降低了ALI和焦磷酸化的严重程度。总之，细胞凋亡在LPS诱导的ALI中起重要作用。ACE2 / Ang（1-7）/ Mas轴负调控发烧，并通过NLRP3抑制保护小鼠免受LPS诱导的ALI。本研究通过提供新的解释，即它可能调节ALI的凋亡，从而扩大了我们对ACE2 / Ang（1-7）/ Mas轴在ALI中的作用的低估。提示ACE2 / Ang（1-7）/ Mas轴参与了LPS诱导的ALI的热解。另外，Ang（1–7）和RES显着降低了NLRP3的水平，而AngII和A779增加了NLRP3的水平。NLRP3基因敲除显着降低了ALI和焦磷酸化的严重程度。总之，细胞凋亡在LPS诱导的ALI中起重要作用。ACE2 / Ang（1-7）/ Mas轴负调控发烧，并通过NLRP3抑制保护小鼠免受LPS诱导的ALI。本研究通过提供新的解释，即它可能调节ALI的凋亡，从而扩大了我们对ACE2 / Ang（1-7）/ Mas轴在ALI中的作用的低估。总之，细胞凋亡在LPS诱导的ALI中起重要作用。ACE2 / Ang（1-7）/ Mas轴负调控发烧，并通过NLRP3抑制保护小鼠免受LPS诱导的ALI。本研究通过提供新的解释，即它可能调节ALI的凋亡，从而扩大了我们对ACE2 / Ang（1-7）/ Mas轴在ALI中的作用的低估。总之，细胞凋亡在LPS诱导的ALI中起重要作用。ACE2 / Ang（1-7）/ Mas轴负调控发烧，并通过NLRP3抑制保护小鼠免受LPS诱导的ALI。本研究通过提供新的解释，即它可能调节ALI的凋亡，从而扩大了我们对ACE2 / Ang（1-7）/ Mas轴在ALI中的作用的低估。