【摘要】 目的 探讨机械损伤后子宫内膜在形态结构、生理功能、纤维化进程及炎症反应方面的病理变化，阐明宫腔粘连的发病机制。方法 选取C57BL/6雌性小鼠42只，随机分为对照组6只、IUA模型组36只。模型组采用钝化后的7号针头刮擦小鼠子宫内膜至子宫充血，内膜粗糙；对照组仅开腹暴露子宫后关腹。分别于术后1天、3天、5天、7天、10天、14天处死小鼠，取子宫组织进行相关检测。HE染色观察子宫内膜厚度及腺体数量；免疫组化、WesternBlot(WB)及实时荧光定量PCR(qRT-PCR)检测增殖标志物Ki-67、血管生成相关指标CD31与VEGF、子宫内膜容受性因子LIF、炎症因子及纤维化标志物FN、α-SMA、COL1A1的表达；Masson染色评估胶原纤维沉积情况。结果 本研究通过多时间点检测发现机械损伤后小鼠子宫内膜指标呈特征性动态变化。形态学上，内膜先于损伤初期(Day1-Day3)短暂增厚，随后逐渐变薄并趋于稳定；功能指标方面，细胞增殖标志物Ki-67表达随术后时间逐渐下降，Day10降至最低；容受性标志物LIF表达波动，最终低于对照组表达。纤维化指标中，胶原纤维沉积随时间逐渐增加，纤连蛋白(FN)持续高表达，I型胶原蛋白(COL1A1)和α-平滑肌肌动蛋白(α-SMA)呈升高趋势。炎症指标中，促炎因子IL-6损伤后显著升高。上述多数指标的变化具有统计学意义(P<0.05)。结论 机械损伤可通过引发持续炎症反应，抑制子宫内膜细胞增殖，形成异常新生血管、诱导纤维化形成，破坏子宫内膜的形态完整性与生理功能，最终导致进行性且难以自我修复的损伤。本研究明确损伤后各指标的动态变化时间节点，为后续靶向干预炎症反应与纤维化进程，探索子宫内膜损伤修复干预时机提供了数据参考。更多还原

【Abstract】 Objective To investigate the pathological changes in the endometrium after mechanical injury, focusing on alterations in tissue morphology, physiological function, fibrotic progression, and inflammatory responses, and to clarify the mechanisms underlying intrauterine adhesion(IUA) development.Methods Forty-two female C57BL/6 mice were included and randomly assigned to a control group(n = 6) and an IUA model group(n = 36).In the model group, the endometrium was mechanically scraped with a blunt No.7 needle until uterine congestion and surface roughness were observed.In the control group, the uterus was surgically exposed and closed without endometrial injury.Uterine tissues were collected at multiple postoperative time points.Hematoxylin and eosin staining was used to assess endometrial thickness and gland count.Immunohistochemistry, Western blotting, and quantitative realtime PCR were performed to evaluate the expression of proliferation marker Ki-67,angiogenesis-related markers CD31 and VEGF,endometrial receptivity factor LIF,inflammatory factors, and fibrosis markers including fibronectin, α-smooth muscle actin, and collagen I.Masson staining was applied to assess collagen fiber deposition.Results Multi-time-point analysis demonstrated that endometrial parameters in mice exhibited distinct dynamic changes after mechanical injury.Morphologically, endometrial thickness transiently increased during the early phase(Days 1-3),then gradually thinned and stabilized.Functionally, expression of the proliferation marker Ki-67 progressively decreased post-surgery, reaching its lowest level on Day 10.The endometrial receptivity marker leukemia inhibitory factor(LIF) showed marked fluctuations and ultimately remained lower than in the control group.Regarding fibrosis, collagen fiber deposition gradually increased over time.Fibronectin(FN) expression remained persistently elevated, while collagen type I(COL1A1) and α-smooth muscle actin(α-SMA) showed an increasing trend.Among inflammatory indicators, the pro-inflammatory cytokine interleukin-6(IL-6) was significantly upregulated after injury.Most of these changes were statistically significant(P<0.05).Conclusion Mechanical injury can induce a sustained inflammatory response, inhibit endometrial cell proliferation, lead to abnormal angiogenesis, and promote fibrosis.These changes disrupt endometrial structural integrity and physiological function, ultimately resulting in irreversible damage.This study clarifies the temporal dynamics of various indicators after injury and provides a reference for identifying optimal intervention time points targeting inflammation and fibrosis, as well as strategies for promoting endometrial repair.更多还原