Abstract：
The primary aim of this study was to explore the impact of diabetes on matrix metalloproteases and tissue inhibitors, crucial factors for successful implantation, and to elucidate the molecular mechanisms that undergo changes in the endometrium and the embryo during diabetic pregnancies. In this investigation, we established a streptozotocin-induced diabetic pregnant rat model. Microarray analysis followed by RT-PCR was utilized to identify gene regions exhibiting expression alterations. Subsequently, we assessed the effects of MMPs and tissue inhibitors using ELISA and immunohistochemistry techniques, in addition to analyzing changes at the genetic level. Diabetes led to the upregulation of MMP3, MMP9, and MMP20 on the 6.5th day of pregnancy, while causing the downregulation of MMP3, MMP9, and MMP11 on the 8.5th day of pregnancy. TIMP1 expression was downregulated on the 8.5th day compared to the control group. No statistically significant differences were observed between the groups regarding other TIMP expressions. KEGG pathway analysis revealed that diabetes induced alterations in the expression of genes associated with certain microRNAs, as well as signaling pathways such as cAMP, calcium, BMP, p53, MAPK, PI3K-Akt, Jak-STAT, Hippo, Wnt, and TNF. Additionally, gene ontology analysis unveiled changes in membrane structures, extracellular matrix, signaling pathways, ion binding, protein binding, cell adhesion molecule binding, and receptor-ligand activity. This study serves as a valuable guide for investigating the mechanisms responsible for complications in diabetic pregnancies. By revealing the early-stage effects of diabetes, it offers insight into the development of new diagnostic and treatment approaches, ultimately contributing to improved patient care.
摘要：
本研究的主要目的是探讨糖尿病对基质金属蛋白酶和组织抑制剂的影响。成功植入的关键因素，并阐明糖尿病妊娠期间子宫内膜和胚胎发生改变的分子机制。在这次调查中,建立链脲佐菌素诱导的糖尿病妊娠大鼠模型。利用微阵列分析和随后的RT-PCR来鉴定表现出表达改变的基因区域。随后，我们使用ELISA和免疫组织化学技术评估MMP和组织抑制剂的作用，除了分析遗传水平的变化。糖尿病导致MMP3、MMP9和MMP20在妊娠第6.5天上调，在妊娠第8.5天引起MMP3，MMP9和MMP11的下调。与对照组相比,TIMP1表达在第8.5天下调。在其他TIMP表达方面，两组之间未观察到统计学上的显着差异。KEGG通路分析显示，糖尿病诱导与某些microRNAs相关的基因表达改变，以及cAMP等信号通路，钙，BMP,p53,MAPK,PI3K-Akt,Jak-STAT,河马,Wnt,和TNF。此外,基因本体论分析揭示了膜结构的变化，细胞外基质，信号通路，离子结合，蛋白质结合，细胞粘附分子结合，和受体-配体活性。这项研究为研究糖尿病妊娠并发症的机制提供了宝贵的指导。通过揭示糖尿病的早期影响，它提供了对新诊断和治疗方法发展的洞察力，最终有助于改善患者护理。
