广地龙干预肌肉减少症的作用机制与研究现状评述

The Mechanism of Action and Current Research Status of Pheretima aspergillum in Intervention for Sarcopenia

摘要: 目的：系统评述广西道地药材广地龙(Pheretima aspergillum)干预肌肉减少症(肌少症)的潜在作用机制、现有证据层级与研究局限，为后续基础与临床转化研究提供客观参考。方法：基于现有文献，梳理广地龙的化学成分、药理活性及肌少症的核心病理机制(蛋白质代谢失衡、慢性炎症、微循环障碍、线粒体功能障碍)，分析二者之间的理论契合点与证据缺口。结果：广地龙含有蚓激酶、活性多肽、琥珀酸及丰富氨基酸等成分，具有改善微循环、抗炎、抗氧化等明确药理活性。理论上，其可通过三大潜在机制干预肌少症：① 改善骨骼肌微循环与营养输送(基于蚓激酶的纤溶、促血管舒张作用及急性缺血模型中的肌保护数据)；② 抑制慢性低度炎症(基于地龙提取物靶向NF-κB通路下调TNF-α、IL-6的体内证据)；③ 辅助优化线粒体功能与能量代谢(基于抗氧化应激及提升运动耐力的实验研究)。然而，核心局限包括：① 直接药效学证据严重匮乏——尚无基于国际公认自然衰老肌少症模型的系统验证，仅有一项2026年小鼠废用性肌萎缩实验显示对非造模侧肌肉重量的临界改善趋势(P = 0.05~0.079)，造模侧未见明确疗效；② 所有机制均源自心脑血管病、肾病等非肌少症模型的外推，缺乏骨骼肌靶向的直接验证；③ 临床研究完全空白，物质基础与量效关系尚未阐明。结论：广地龙具备干预肌少症的理论合理性与潜在开发价值，尤其在“活血通络”改善微循环方面呈现差异化优势。但当前研究处于极初步阶段，尚未形成任何级别的循证证据链。未来必须优先完成自然衰老肌少症模型的系统药效学与靶向机制验证，明确核心质量标志物，再逐步推进临床探索，方可评估其真实临床适用性。

Abstract: Objective: To systematically review the potential mechanisms, existing evidence, and research limitations of Guang Dilong (Pheretima aspergillum), a genuine medicinal from Guangxi, in the intervention of sarcopenia, and to provide an objective reference for future basic and translational research. Methods: Based on available literature, the chemical composition and pharmacological activities of P. aspergillum were analyzed alongside the core pathological mechanisms of sarcopenia (protein metabolism imbalance, chronic inflammation, microcirculatory dysfunction, mitochondrial dysfunction). The theoretical alignment and evidence gaps between them were evaluated. Results: P. aspergillum contains lumbrokinase, bioactive peptides, succinic acid, and abundant amino acids, exhibiting well‑defined pharmacological activities including microcirculation improvement, anti‑inflammation, and anti‑oxidation. Theoretically, it may intervene in sarcopenia via three potential mechanisms: ① Improving skeletal muscle microcirculation and nutrient supply (based on the fibrinolytic and vasodilatory effects of lumbrokinase and muscle protection data from acute ischemia models); ② Suppressing chronic low‑grade inflammation (based on in vivo evidence that earthworm extract down‑regulates TNF‑α and IL‑6 via the NF‑κB pathway); ③ Auxiliary optimization of mitochondrial function and energy metabolism (based on anti‑oxidative stress and exercise endurance studies). However, major limitations include: ① Severe lack of direct pharmacodynamic evidence—no systematic validation using internationally recognized natural aging sarcopenia models; only one 2026 mouse disuse atrophy study showed a trend of improvement in non‑casted side muscle weight (P = 0.05~0.079), with no significant effect on the casted side; ② All proposed mechanisms are extrapolated from non‑sarcopenia models (e.g., cardiovascular, renal diseases) without direct skeletal muscle‑targeted validation; ③ Complete absence of clinical studies, and unclear active constituents as well as dose‑response relationships. Conclusion: Pheretima aspergillum has theoretical rationale and potential value for sarcopenia intervention, particularly with its differentiated advantage in promoting blood circulation and removing stasis to improve microcirculation. Nevertheless, current research remains at a very preliminary stage, with no evidence chain of any grade established. Future studies must prioritize systematic pharmacodynamic evaluation and target‑specific mechanistic validation using natural aging sarcopenia models, identify key quality markers, and then gradually advance to clinical exploration before its true clinical applicability can be assessed.