Zhou Lina, Liang Hui, Chen Yulin, Hu Kai, Liu Xixia
The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
J Orthop Surg Res. 2025 Jun 2;20(1):556. doi: 10.1186/s13018-025-05977-9.
This study integrates Mendelian randomization (MR) analysis with animal experiments to systematically evaluate the therapeutic efficacy of varying concentrations of hypertonic dextrose on tendon injury and elucidate the underlying mechanisms in the context of tendon repair.
The SwissTargetPrediction database was utilized to identify potential molecular targets of dextrose. Two-sample MR analysis was performed to investigate the causal relationships between the identified targets and Achilles tendinopathy. Comprehensive in vivo experiments that included behavioral tests, histological examination (hematoxylin‒eosin staining), and molecular analyses (Western blotting and RT‒qPCR) were conducted to validate the MR findings.
MR analysis revealed a significant causal association between dextrose-mediated effects and IGF-2R expression in the context of Achilles tendinopathy. In vivo studies demonstrated that tendon injury significantly impaired motor function in a rat model, with notable improvements observed after dextrose intervention. Histopathological analysis revealed that injured tendons presented disorganized collagen fiber arrangement, enhanced neovascularization, and increased cellular proliferation. Dextrose treatment at both 15% and 25% concentrations significantly improved collagen fiber organization, resulting in more compact and parallel fiber alignment. Furthermore, dextrose intervention significantly modulated the expression of molecular markers, including reduced type III collagen expression, upregulated vascular endothelial growth factor expression, and downregulated IGF-2R mRNA expression. Notably, 25% dextrose solution demonstrated superior efficacy, significantly increasing the expression of SCX, type I collagen, and transforming growth factor-β1.
Hypertonic dextrose downregulates IGF-2R expression, upregulates vascular endothelial growth factor and transforming growth factor-β1 expression, modulates collagen synthesis, increases type I collagen content, and accelerates tendon healing. Among the tested concentrations, 25% hypertonic glucose yielded the best therapeutic outcomes.
本研究将孟德尔随机化（MR）分析与动物实验相结合，系统评估不同浓度高渗葡萄糖对肌腱损伤的治疗效果，并阐明肌腱修复背景下的潜在机制。
利用SwissTargetPrediction数据库确定葡萄糖的潜在分子靶点。进行两样本MR分析，以研究已确定靶点与跟腱病之间的因果关系。开展包括行为测试、组织学检查（苏木精-伊红染色）和分子分析（蛋白质免疫印迹和逆转录定量聚合酶链反应）在内的全面体内实验，以验证MR研究结果。
MR分析显示，在跟腱病背景下，葡萄糖介导的效应与IGF-2R表达之间存在显著因果关联。体内研究表明，肌腱损伤在大鼠模型中显著损害运动功能，葡萄糖干预后观察到明显改善。组织病理学分析显示，损伤肌腱的胶原纤维排列紊乱、新生血管形成增加和细胞增殖增多。15%和25%浓度的葡萄糖处理均显著改善了胶原纤维组织，使纤维排列更紧密且平行。此外，葡萄糖干预显著调节了分子标志物的表达，包括III型胶原表达降低、血管内皮生长因子表达上调和IGF-2R mRNA表达下调。值得注意的是,25%葡萄糖溶液显示出更好的疗效，显著增加了SCX、I型胶原和转化生长因子-β1的表达。
高渗葡萄糖下调IGF-2R表达，上调血管内皮生长因子和转化生长因子-β1表达，调节胶原合成，增加I型胶原含量，并加速肌腱愈合。在所测试的浓度中，25%高渗葡萄糖产生了最佳治疗效果。
