研究领域：药理学 生物化学 医学

关键字：新型稻米肽 抗痛风活性 高尿酸血症小鼠黄 嘌呤氧化酶 尿酸转运蛋白1 NLRP3炎性体 足肿胀 炎症反应

痛风作为一种代谢性疾病，严重影响患者正常生活，在现代社会中发病率日益升高。然而，现有药物尚无法完全满足临床需求。本研究从去壳水稻（Oryza sativa）果实水提物中分离并鉴定出一种新型短肽——稻源性肽-2（rice-derived-peptide-2, RDP2），其序列为AAAAGAMPK-NH₂，分子量为785.97 Da，无明显毒性且稳定性优异。实验结果表明，RDP2最低有效剂量为5 μg·kg⁻¹，可显著降低高尿酸血症小鼠血清尿酸水平，其机制涉及抑制黄嘌呤氧化酶活性及尿酸转运蛋白1（urate transporter 1）的表达；同时，RDP2可通过抑制NLRP3炎症小体活化，缓解肾脏损伤。此外，RDP2亦可减轻单钠尿酸盐晶体皮下注射诱导的小鼠足跖肿胀及炎症反应。综上所述，本研究获得了一种可作用于痛风全过程的新型多肽：不仅可降低高尿酸血症小鼠的血尿酸水平与肾脏损伤，还可缓解急性痛风发作相关的炎症反应，从而为抗痛风药物的研发提供了新的多肽分子模板。As a metabolic disease, gout, which seriously affects the normal life of patients, has become increasingly common in modern society. However, the existing medicines cannot completely meet the clinical needs. In the current study, a novel short peptide (named rice-derived-peptide-2 (RDP2), AAAAGAMPK-NH2, 785.97 Da) was isolated and identified from water extract of shelled Oryza sativa fruits, without toxic side effects but excellent stability. Our results indicated that RDP2 (the minimum effective concentration is 5 μg kg−1) induced a significant reduction in serum uric acid levels in hyperuricemic mice via suppressing xanthine oxidase activity and urate transporter 1 expression, as well as alleviated renal damage through inhibiting the activation of NLRP3 inflammasome. In addition, RDP2 can also alleviate paw swelling and inflammatory reactions in mice after subcutaneous injection of monosodium urate crystals. As mentioned above, we obtained a novel peptide which could work through all stages of gout, not only reducing uric acid levels and renal damage in hyperuricemic mice, but also alleviating inflammatory responses associated with acute gout attack, and thus provided a new peptide molecular template for the development of anti-gout drugs.