| 张璟璐,吴一平,周文宇,郑慧婷,金奕安.鸢尾素通过上调Wnt/β-catenin通路对肌少症小鼠的保护作用.[J].中南医学科学杂志.,2024,(4):529-533. |
| 鸢尾素通过上调Wnt/β-catenin通路对肌少症小鼠的保护作用 |
| Protection of irisin on sarcopenia mice by up-regulating Wnt/β-catenin pathway |
| 投稿时间：2024-03-13 修订日期：2024-06-18 |
| DOI：10.15972/j.cnki.43-1509/r.2024.04.006 |
| 中文关键词: 鸢尾素 Wnt/β-catenin通路 肌少症 小鼠 |
| 英文关键词:irisin Wnt/β-catenin pathway sarcopenia mice |
| 基金项目:广东省医学科学技术研究基金项目(C2021040) |
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| 中文摘要: |
| 目的探讨鸢尾素治疗肌少症小鼠的作用机制。 方法将雄性SPF级野生C57小鼠随机分为对照组、模型组、鸢尾素组、鸢尾素+Wnt/β-连环蛋白(β-catenin)通路抑制剂组(鸢尾素+XAV939组),每组28只。采用抓力检测、抓绳时间及游泳实验检测各组小鼠行为学指标水平。比较各组腓肠肌湿重比；HE染色观察各组腓肠肌病理学形态改变。采用Western blotting检测各组自噬相关蛋白(Beclin1、LC3Ⅱ/Ⅰ)和通路相关蛋白(Wnt、β-catenin)的表达水平。采用实时荧光定量PCR法检测线粒体分裂融合相关基因动力相关蛋白1(Drp1)、线粒体融合蛋白2(Mfn2)及视神经萎缩蛋白1(Opa1)表达水平。 结果对照组小鼠腓肠肌组织排列整齐,无炎症细胞浸润及水肿坏死情况；模型组小鼠腓肠肌组织结构受损严重,组织排列紊乱,可见大量炎症细胞浸润及肌纤维溶解情况；鸢尾素组小鼠腓肠肌组织较模型组明显改善；鸢尾素+XAV939组与模型组相似。与对照组相比,模型组小鼠抓力、Beclin1、LC3Ⅱ/Ⅰ、Drp1 mRNA、Wnt、β-catenin表达降低(P＜0.05),抓绳和游泳时间、腓肠肌湿重比减少(P＜0.05),Mfn2、Opa1 mRNA表达升高(P＜0.05)；与模型组相比,鸢尾素组上述指标得以递转(P＜0.05)；与鸢尾素组相比,鸢尾素+XAV939组上述指标变化同模型组趋势(P＜0.05)。 结论鸢尾素可能通过上调Wnt/β-catenin通路改善肌少症小鼠自噬,促进线粒体分裂,抑制线粒体融合,从而起到一定的肌保护作用。 |
| 英文摘要: |
| AimTo explore the mechanism of irisin in treating sarcopenia mice. MethodsMale SPF wild C57 mice were randomly divided into the control group, model group, irisin group, irisin+Wnt/β-catenin pathway inhibitor group (irisin+XAV939 group), with 28 mice in each group. The level of behavioral indexes of mice in each group was detected by grasping force detection, rope grasping time and swimming experiment. The wet to weight ratio of gastrocnemius muscle in each group was compared. HE staining was used to observe the pathological changes of gastrocnemius muscle in each group. The expression levels of autophagy-related proteins (Beclin1, LC3Ⅱ/Ⅰ) and pathway-related proteins (Wnt, β-catenin) were detected by Western blotting.Real-time fluorescence quantitative PCR was used to detect the expression levels of mitotic fusion related-genes, such as dynamic related protein 1 (Drp1), mitochondrial fusion protein 2 (Mfn2) and optic atrophy protein 1 (Opa1). ResultsIn the control group, the gastrocnemius tissue was arranged neatly, and there was no inflammatory infiltration, edema or necrosis. In the model group, the gastrocnemius muscle tissue structure was seriously damaged, the tissue arrangement was disordered, and a large number of inflammatory cells infiltrated and muscle fibers dissolved. The gastrocnemius tissue in irisin group was significantly improved compared with those in model group. Irisin+XAV939 group is similar to the model group. Compared with the control group, the grasping power, the expression of Beclin1, LC3Ⅱ/Ⅰ, Drp1 mRNA, Wnt and β-catenin in the model group were decreased (P＜0.05), the time of grasping rope and swimming,the wet to weight ratio of gastrocnemius were decreased (P＜0.05), and the expressions of Mfn2 and Opa1 mRNA were increased (P＜0.05). Compared with the model group, the levels of the above indicators in the irisin group were reversed(P＜0.05). Compared with the irisin group, the changes in the above indicators in the irisin+XAV939 group showed the same trend as the model group (P＜0.05). ConclusionIrisin may improve autophagy, promote mitochondrion division and inhibit mitochondrion fusion in mice with sarcopenia by up-regulating Wnt/β-catenin pathway, thus playing a certain role in muscle protection. |
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