Hu Qin, Liu Haoran, Wang Ruiyu, Yao Li, Chen Shikun, Wang Yang, Lv Chuanzhu
Emergency and Trauma College, Hainan Medical University, Haikou, People's Republic of China.
Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Haikou, People's Republic of China.
J Inflamm Res. 2024 Jan 9;17:153-170. doi: 10.2147/JIR.S441141. eCollection 2024.
Acute lung injury (ALI) is a severe pulmonary disease characterized by damage to the alveoli and pulmonary blood vessels, leading to severe impairment of lung function. Studies on the effect of capsaicin (8-methyl-N-geranyl-6-nonamide, CAP) on lipopolysaccharide (LPS)-induced ALI in bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B) are still limited. This study aimed to investigate the effect and specific mechanism by which CAP improves LPS-induced ALI.
The present study investigated the effect of CAP and the potential underlying mechanisms in LPS-induced ALI in vitro and vivo via RNA sequencing, Western blotting (WB), quantitative real-time reverse transcription PCR (qRT‒PCR), enzyme-linked immunosorbent assay (ELISA), and transmission electron microscopy (TEM). The TRPV1 inhibitor AMG9810 and the AKT agonist SC79 were used to confirm the protective effect of the TRPV1/AKT axis against ALI. The autophagy agonist rapamycin (Rapa) and the autophagy inhibitors 3-methyladenine (3-MA) and bafilomycin A1 (Baf-A1) were used to clarify the characteristics of LPS-induced autophagy.
Our findings demonstrated that CAP effectively suppressed inflammation and autophagy in LPS-induced ALI, both in vivo and in vitro. This mechanism involves regulation by the TRPV1/AKT signaling pathway. By activating TRPV1, CAP reduces the expression of P-AKT, thereby exerting its anti-inflammatory and inhibitory effects on pro-death autophagy. Furthermore, prior administration of CAP provided substantial protection to mice against ALI induced by LPS, reduced the lung wet/dry ratio, decreased proinflammatory cytokine expression, and downregulated LC3 expression.
Taken together, our results indicate that CAP protects against LPS-induced ALI by inhibiting inflammatory responses and autophagic death through the TRPV1/AKT signaling pathway, presenting a novel strategy for ALI therapy.
急性肺损伤（ALI）是一种严重的肺部疾病，其特征是肺泡和肺血管受损，导致肺功能严重受损。关于辣椒素（8-甲基-N-香叶基-6-壬酰胺，CAP）对经Ad12-SV40 2B转化的支气管上皮细胞（BEAS-2B）中脂多糖（LPS）诱导的ALI影响的研究仍然有限。本研究旨在探讨CAP改善LPS诱导的ALI的作用及其具体机制。
本研究通过RNA测序、蛋白质免疫印迹法（WB）、定量实时逆转录PCR（qRT-PCR）、酶联免疫吸附测定（ELISA）和透射电子显微镜（TEM），在体外和体内研究了CAP对LPS诱导的ALI的影响及其潜在机制。使用TRPV1抑制剂AMG9810和AKT激动剂SC79来证实TRPV1/AKT轴对ALI的保护作用。使用自噬激动剂雷帕霉素（Rapa）和自噬抑制剂3-甲基腺嘌呤（3-MA）及巴弗洛霉素A1（Baf-A1）来阐明LPS诱导的自噬特征。
我们的研究结果表明，CAP在体内和体外均能有效抑制LPS诱导的ALI中的炎症和自噬。该机制涉及TRPV1/AKT信号通路的调节。通过激活TRPV1，CAP降低了P-AKT的表达，从而对促死亡自噬发挥其抗炎和抑制作用。此外，预先给予CAP可显著保护小鼠免受LPS诱导的ALI，降低肺湿/干比，减少促炎细胞因子表达，并下调LC3表达。
综上所述，我们的结果表明，CAP通过TRPV1/AKT信号通路抑制炎症反应和自噬性死亡，从而预防LPS诱导的ALI，为ALI治疗提供了一种新策略。
