目的·建立新生大鼠发育肌腱去应力模型，通过生物信息学分析可能的分子机制。方法·选择60只出生10 d的SD大鼠，切断左侧跟腱作为实验组（去应力组），钳夹损伤右侧跟腱作为对照组（力刺激组）。手术处理后第10日和第20日收集肌腱组织样本，大体观察肌腱发育情况；苏木精-伊红（H-E）染色观察肌腱组织学结构变化.；透射电子显微镜观察肌腱胶原超微结构的变化；免疫组织化学检测肌腱组织中CD31的表达。运用蛋白质谱分析技术获得2个时间点的组间差异表达蛋白，并对差异蛋白行GO分析、KEGG富集分析、蛋白互作（protein-protein interaction，PPI）网络分析。结果·去应力组肌腱呈现组织膨大及充血的大体观，以及肌腱组织结构紊乱、胶原纤维不成熟的病理改变。透射电子显微镜下观察到去应力组肌腱胶原纤维发育和成熟障碍；术后第20日，去应力组肌腱胶原纤维直径显著小于力刺激组（P=0.001）。免疫组织化学染色结果显示肌腱呈血管化改变。蛋白质谱分析结果显示：术后第10日鉴定出差异表达蛋白1 865种，其中1 835种蛋白上调；术后第20日鉴定出差异表达蛋白965种，其中837种蛋白上调。GO分析结果显示，上调的差异表达蛋白主要参与细胞内蛋白运输、蛋白质稳定性、mRNA剪接、蛋白质折叠、蛋白质导入细胞核等生物过程。KEGG分析结果显示，血管内皮生长因子（VEGF）信号通路、哺乳动物雷帕霉素靶蛋白（mTOR）信号通路、吞噬作用等信号通路增强。PPI分析结果显示，Akt1、Hspa4、Hspa5、Eef2、ACTC1、RhoA等多种蛋白表达上调。结论·去应力可激活细胞内多条信号通路，引起组织血管化、胶原发育异常等，造成肌腱退化性病理改变。

Objective ·To explore relevant molecular mechanisms of the stress deprivation model of newborn rats by using bioinformatics analysis. Methods ·A total of 60 SD rats (10 d post-natal) were enrolled in the study. Those the left Achilles tendon of which was severed were chosen as the experimental group (stress deprivation group), and the right Achilles tendon of which was injured by clamping were chosen as the control group (stress group). On the 10th and 20th day after treatment, tissue samples were collected for gross observation of the tendon development, histological staining of the tendon structure, transmission electron microscope observation of the tendon ultrastructure and immunohistochemical analysis of CD31 expression. Differentially expressed proteins between the two groups at two time points were obtained by using protein mass spectrometry, and GO and KEGG enrichment analysis as well as protein-protein interaction (PPI) network anlysis were performed on differential proteins. Results ·The stress-deprived tendon showed tissue enlargement and congestion, disorganized tendon tissue structure and immature collagen fibers. Transmission electron microscopy showed that the development and maturation of collagen fibrils were significantly impaired in the experimental group, and the diameter of collagen fibrils of the severed tendon became thinner on the 20th day after treatment (P=0.001). Immunohistochemistry showed that the severed tendon was relatively vascularized. The results of protein mass spectrometry analysis showed there were 1 865 and 965 differentially expressed proteins on the 10th and 20th day after treatment, including 1 835 and 837 upregulated proteins respectively. GO analysis showed that the upregulated proteins were involved in biological processes such as intracellular protein transport, protein stabilization, mRNA splicing via spliceosome, protein folding and protein import into nucleus. KEGG analysis indentified enhancement of vascular endothelial growth factor (VEGF) signal pathway, mammalian target of rapamycin (mTOR) signal pathway, endocytosis and other signal pathways in the experimental group. PPI network analysis showed various upregulated proteins including Akt1, Hspa4, Hspa5, Eef2, ACTC1 and RhoA. Conclusion ·Stress deprivation can activate multiple signal pathways in tendon cells and lead to tissue vascularization, abnormal collagen development, etc., resulting in degenerative pathological changes of tendons.