基于Wnt/β-catenin通路探讨三七复方对D-半乳糖致衰老大鼠肾脏的抗氧化作用及机制*

作者：王 祯1，李亚金2，沈奕玮1，王倍翔1，董媛媛2，金振辉1，王玉英1，王景霞1

单位：1.北京中医药大学，北京 100029； 2.新疆医科大学，新疆 乌鲁木齐 830011

引用：引用：王祯，李亚金，沈奕玮，王倍翔，董媛媛，金振辉，王玉英，王景霞.基于Wnt/β-catenin通路探讨三七复方对D-半乳糖致衰老大鼠肾脏的抗氧化作用及机制[J].中医药导报,2025,31(12):1-7.

DOI：10.13862/j.cn43-1446/r.2025.12.001

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摘要：

目的：评价三七复方对肾脏的抗氧化及保护作用，并探究基于Wnt/β-catenin通路的抗氧化延缓衰老的作用机制。方法：将72只雄性SD大鼠按照体质量随机分为空白组、模型组、维生素E组、三七复方低剂量组、三七复方中剂量组、三七复方高剂量组，每组12只。除空白组外,其余各组大鼠连续4周腹腔注射D-半乳糖以制备衰老大鼠模型。造模期间，空白组、模型组大鼠每天灌胃蒸馏水，维生素E组大鼠灌胃维生素E溶液，三七复方低、中、高剂量组大鼠分别灌胃低、中、高剂量三七复方药液，连续4周。给药期间每日观察大鼠精神状态和毛色，每周检测大鼠体质量。给药结束后观测大鼠肾脏系数、肾一般损伤情况（包括肾功能指标BUN、Cr、UA）、肾脏氧化应激水平（过氧化产物MDA、8-OHdG）、抗氧化系统指标（T-SOD活力、GSH-Px活力、CAT活力、T-AOC、GSH/GSSG）、肾组织形态结构（HE观察）以及肾组织中Wnt/β-catenin通路相关蛋白（Wnt4、GSK-3β、p-GSK-3β、β-catenin、c-Myc）相对表达量。结果：使用D-半乳糖造模后，与空白组相比，大鼠肾脏系数降低、肾功能减退、过氧化产物（MDA和8-OHdG）含量明显升高、肾中抗氧化指标（T-SOD活力、GSH-Px活力、CAT活力、T-AOC、T-GSH/GSSG比值）明显降低，肾脏组织内Wnt4、p-GSK3β、β-catenin和c-Myc蛋白表达量增加，GSK3β蛋白表达量下降，p-GSK3β/GSK3β上升；与模型组相比，三七复方组大鼠肾功能显著改善，氧化损伤减轻，机体抗氧化能力提高，肾脏组织内Wnt4、p-GSK3β、β-catenin和c-Myc蛋白表达量减少，p-GSK3β/GSK3β降低。结论：三七复方能够通过抑制D-半乳糖致衰老模型大鼠的氧化应激反应，减轻机体氧化损伤，减轻肾损伤，起到延缓衰老的作用。三七复方可能通过抑制Wnt/β-catenin通路，促进β-catenin的降解，减少β-catenin进入细胞核与TCF/LEF结合，抑制TCF/LEF调控的c-Myc基因表达，减少ROS的产生，降低机体氧化损伤，起到抗氧化延缓衰老的作用。

关键词：衰老；抗氧化；三七复方；Wnt/β-catenin通路；氧化应激；大鼠

Abstract：

Objective: To evaluate the antioxidant and protective effects of Panaxnotoginseng formula (PNF) on the kidneys and to explore its mechanism in delaying aging through antioxidant effects via the Wnt/β-catenin pathway. Methods: Totally 72 male Sprague-Dawley (SD) rats were randomly divided into control group, model group, vitamin E group, PNF low dose group, PNF medium dose group, and PNF high dose group, 12 rats in each group, based on body weight. Except for the control group, all other groups received daily intraperitoneal injections of D-galactose for four weeks to establish an aging model. During modeling, the control and model groups were given distilled water via oral gavage daily. The vitamin E group received vitamin E solution. The PNF low dose group, PNF medium dose group, and PNF high dose group received low dose, medium dose and high dose of PNF solution respectively for four weeks. The mental state and coat color of the rats were observed daily, and body weight was measured weekly. After treatment, kidney indices, renal function (BUN, Cr, UA), oxidative stress markers (MDA and Q18-OHdG), antioxidant indicators (T-SOD, GSH-Px, CAT, T-AOC and GSH/GSSG), renal morphology (HE staining), and protein expression levels of Wnt/β-catenin pathway components (Wnt4, GSK-3β, p-GSK-3β, β-catenin, c-Myc) were measured. Results: After D-galactose modeling, compared with the control group, the model group showed a decreased kidney index, impaired renal function, significantly increased levels of peroxidation products (MDA and 8-OHdG), and significantly decreased antioxidant indicators (T-SOD activity, GSH-Px activity, CAT activity, T-AOC, and GSH/GSSG ratio). The protein expression of Wnt4, p-GSK-3β, β-catenin, and c-Myc in renal tissue increased, while GSK-3β expression decreased and the p-GSK-3β/GSK-3β ratio increased. Compared with the model group, PNF group significantly improved renal function, alleviated oxidative damage, enhanced systemic antioxidant capacity, reduced the protein expression of Wnt4, p-GSK-3β, β-catenin, and c-Myc, and decreased the p-GSK-3β/GSK-3β ratio. Conclusion: Panaxnotoginseng formula can mitigate oxidative stress, reduce oxidative damage and renal injury, thereby exerting an anti-aging effect in D-galactose-induced aging model rats. The mechanism may involve inhibiting the Wnt/β-catenin pathway, promoting the degradation of β-catenin, reducing its translocation into the nucleus and binding to TCF/LEF, and suppressing the expression of the TCF/LEF-regulated c-Myc gene. This leads to reduced ROS production, decreased systemic oxidative damage, and ultimately contributes to its antioxidant and anti-aging effects.

Key words：aging; antioxidant; Panaxnotoginseng formula; Wnt/β-catenin pathway; oxidative stress; rat

发布时间：2025-12-31

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