基于“毒损肾络”理论探讨高尿酸血症肾纤维化的病理机制及中药干预策略

Discussion on the Pathological Mechanism of Renal Fibrosis in Hyperuricemia and Intervention Strategies of Traditional Chinese Medicine Based on the Theory of “Toxin Damaging Kidney Collaterals”

摘要: 高尿酸血症是慢性肾脏病进展的独立危险因素，长期尿酸控制不佳可导致肾小管间质纤维化，最终发展为终末期肾病。其病理机制涉及尿酸代谢紊乱、炎性损伤、氧化应激及上皮–间质转化等多重环节。中医学将高尿酸血症肾纤维化归为“溺毒”、“肾痹”范畴，核心病机可概括为“毒损肾络”，即脾肾亏虚、湿浊瘀毒内生，蕴结肾络形成纤维化瘢痕。文章基于“毒损肾络”理论，系统梳理高尿酸血症肾纤维化的病理机制，从尿酸转运体失调所致的“浊毒内停”、NLRP3炎症小体激活介导的“毒火伤络”、氧化应激引发的“毒邪化热”、TGF-β1/Smad通路驱动的上皮–间质转化及微血管损伤导致的“络脉瘀阻”四个层面，阐释“毒–瘀–络–积”的病变演变规律。在此基础上，综述单味中药及复方干预策略的研究进展，体现中医药“祛毒–化瘀–通络–修复–扶正”的整体治疗观。与此同时，当前研究仍面临病证结合动物模型缺乏、临床证据等级不高等局限，未来应借助组学技术和网络药理学深入揭示“毒损肾络”的现代生物学内涵，为从该理论论治高尿酸血症肾纤维化提供更充分的科学依据。

Abstract: Hyperuricemia is an independent risk factor for the progression of chronic kidney disease. Poorly controlled uric acid levels can lead to tubular interstitial fibrosis, ultimately resulting in end-stage renal disease. The pathological mechanisms involved encompass multiple interconnected processes, including uric acid metabolic disorders, inflammatory injury, oxidative stress, and epithelial-mesenchymal transition. Within the framework of traditional Chinese medicine, hyperuricemia-induced renal fibrosis falls under the categories of “retained turbid toxin” and “kidney impediment”, with the core pathogenesis summarized as “toxin damaging kidney collaterals”—a condition arising from spleen-kidney deficiency and the endogenous accumulation of damp-turbidity and stasis-toxin, which congeal in the kidney collaterals and ultimately form fibrotic scars. Based on the “toxin damaging kidney collaterals” theory, this review systematically delineates the pathological mechanisms of hyperuricemia-induced renal fibrosis. The evolutionary pattern of “toxin-stasis-collateral-accumulation” is elucidated from four perspectives: “internal stagnation of turbid-toxin” resulting from dysregulated urate transporters, “toxic fire damaging collaterals” mediated by NLRP3 inflammasome activation, “toxin transforming into heat” triggered by oxidative stress, and epithelial-mesenchymal transition driven by the TGF-β1/Smad pathway coupled with “collateral obstruction” caused by microvascular injury. Furthermore, research progress on intervention strategies involving single herbs and formulas is reviewed, reflecting the holistic therapeutic approach of “eliminating toxin-resolving stasis-unblocking collaterals-restoring collateral integrity-reinforcing vital energy” in traditional Chinese medicine. Meanwhile, current research remains limited by the lack of disease-syndrome combination animal models and the relatively low level of clinical evidence. Future investigations should employ omics technologies and network pharmacology to further elucidate the modern biological connotation of “toxin damaging kidney collaterals”, thereby providing a more substantial scientific basis for the treatment of hyperuricemia-induced renal fibrosis based on this theoretical framework.