高效抗炎、抗氧化，亚精胺成为治疗炎症性疾病的种子选手

高效抗炎、抗氧化，亚精胺成治疗炎症性疾病的种子选手

【文献解读】

韩国东义大学医学院抗衰老研究中心Yung Hyun Choi课题组研究发现，亚精胺在脂多糖刺激的巨噬细胞和斑马鱼中可有效抑制炎症细胞因子的产生和活性氧的积累，提示了亚精胺在炎症性疾病中的治疗潜力。该研究成果发表于Biomolecules & Therapeutics杂志。

研究人员首先选择巨噬细胞进行实验，用脂多糖刺激产生炎症反应，表现在一氧化氮和前列腺素E2产生增加，它们对应的合成酶一氧化氮合酶和环氧化酶2表达增加，促炎细胞因子如肿瘤坏死因子α和白介素1β分泌也显著增加。此外，脂多糖刺激后也观察到细胞内活性氧的积累。亚精胺处理以剂量依赖性的方式抑制了一氧化氮和前列腺素E2的分泌、相关合成酶的表达和炎症水平。800Μm亚精胺使肿瘤坏死因子α含量由约1200pg/mL降至约300pg/mL，白介素1β由约900pg/mL降至约250pg/mL。活性氧产生也显著被抑制。

研究人员随后在斑马鱼中进一步展开了实验，脂多糖诱导的一氧化氮和活性氧的产生都被亚精胺逆转。此外，脂多糖导致了斑马鱼卵黄囊发生中性粒细胞浸润，表皮中发生巨噬细胞浸润。用亚精胺治疗可显著减少这两种免疫细胞的迁移。

研究人员指出，慢性炎症和氧化应激是衰老和许多年龄相关疾病（如心血管疾病、类风湿性关节炎、阿尔兹海默病）发生的重要原因。研究发现，亚精胺表现出高效的抗炎和抗氧化作用，说明它在改善和治疗相关疾病方面非常有应用潜力。

【文献节选】

Spermidine is a naturally occurring polyamine compound that has recently emerged with anti-aging properties and suppresses inflammation and oxidation. However, its mechanisms of action on anti-inflammatory and antioxidant effects have not been fully elucidated. In this study, the potential of spermidine for reducing pro-inflammatory and oxidative effects in lipopolysaccharide (LPS)-stimulated macrophages and zebrafish was explored. Our data indicate that spermidine significantly inhibited the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), and cytokines including tumor necrosis factor-α and interleukin-1β in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects of spermidine accompanied by a marked suppression in their regulatory gene expression at the transcription levels. Spermidine also attenuated the nuclear translocation of NF-κB p65 subunit and reduced LPS-induced intracellular accumulation of reactive oxygen species (ROS) in RAW 264.7 macrophages. Moreover, spermidine prevented the LPS-induced NO production and ROS accumulation in zebrafish larvae and was found to be associated with a diminished recruitment of neutrophils and macrophages. Although more work is needed to fully understand the critical role of spermidine on the inhibition of inflammation-associated migration of immune cells, our findings clearly demonstrate that spermidine may be a potential therapeutic intervention for the treatment of inflammatory and oxidative disorders.