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| 糖尿病合并妊娠通过PI3K/AKT抑制胎盘血管生成损伤影响大鼠子代宫内生长 |
| Diabetes complicating pregnancy impairs placental angiogenesis via PI3K/AKT inhibition, affecting intrauterine growth in rat offspring |
| 投稿时间：2025-12-03 |
| DOI：10.3969/j.issn.1000-0399.2026.09.001 |
| 中文关键词: 糖尿病合并妊娠 胎盘 磷脂酰肌醇3-激酶/蛋白激酶B 宫内生长受限 |
| 英文关键词: Diabetes in pregnancy Placenta Phosphatidylinositol-3-kinase/protein kinase B Intrauterine growth restriction |
| 基金项目:贵州医科大学附属医院国家自然科学基金(NSFC)青年基金培育计划项目{编号:gyfynsfc[2023]-20};2025年度省基础研究计划(自然科学)面上项目{编号:黔科合基础MS[2025]425};国家自然科学基金地区科学基金项目(编号:82260165);国家自然科学基金青年科学基金项目(编号:82300920);国家自然科学基金地区科学基金项目(编号:82560169);贵州省科学技术协会“新质黔沿”引领项目(编号:QKX2026-KC-YZ045) |
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| 中文摘要: |
| 目的 构建糖尿病合并妊娠动物模型，探讨糖尿病合并妊娠导致子代宫内生长受限的潜在机制。方法 选取16只SD大鼠，根据随机数字表法将大鼠分为糖尿病合并妊娠组（PGDM组）和正常对照组（NC组），每组8只。PGDM组腹腔注射45 mg/kg链脲佐菌素以构建糖尿病模型，之后与SD雄鼠合笼；NC组腹腔注射等剂量柠檬酸钠缓冲液后与SD雄鼠合笼；动态观察两组孕鼠随机血糖和体质量变化；记录新生鼠出生体质量、胎盘重量、出生数量和存活数量；HE染色观察胎盘形态；免疫组化检测胎盘血管生成相关因子、胎盘磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)表达；蛋白印迹法检测PI3K/AKT和CD31蛋白表达情况；聚合酶链式反应（PCR）检测低氧诱导因子-1(HIF-1)和血管内皮生长因子（VEGF） mRNA表达情况。结果 8只大鼠均成功构建糖尿病合并妊娠模型。PGDM组体质量增长慢于NC组且随机血糖持续高于16.7 mmol/L，两组SD大鼠差异存在统计学意义（P<0.05）。PGDM组新生鼠出生体质量、胎盘重量、出生率及存活率均低于NC组（P<0.05）。HE染色显示，PGDM组胎盘绒毛结构异常，血管粗细不均；NC组毛细血管分布均匀，边缘清晰。PGDM组血管生成因子、PI3K/AKT的蛋白、p-PI3K/PI3K与p-AKT/AKT的比值及mRNA的表达低于NC组（P<0.05）。结论 PGDM组胎盘通过抑制PI3K/AKT通路蛋白表达，损伤胎盘血管生成，最终导致子代生长受限。 |
| 英文摘要: |
| Objective To establish an animal model of diabetes complicating pregnancy and investigate the potential mechanism by which diabetes complicating pregnancy leads to intrauterine growth restriction in offspring. Methods Sixteen Sprague-Dawley(SD) rats were randomly divided into a diabetes complicating pregnancy group(PGDM group) and a normal control group(NC group) using a random number table method, with 8 rats in each group. The PGDM group received an intraperitoneal injection of 45 mg/kg streptozotocin(STZ) to establish the diabetes model and was subsequently mated with SD male rats; the NC group received an intraperitoneal injection of an equivalent dose of sodium citrate buffer and was then mated with SD male rats. Random blood glucose and body weight changes in pregnant rats were dynamically observed. The birth weight, placental weight, litter size, and number of surviving offspring were recorded. Placental morphology was observed using HE staining. The expression of placental angiogenesis-related factors and phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT) was detected by immunohistochemistry. The protein expression of placental PI3K/AKT and CD31 was detected by Western blotting. The mRNA expression levels of HIF-1 and VEGF were detected by quantitative real-time polymerase chain reaction(qRT-PCR). Results The PGDM model was successfully established in all 8 rats. The body weight gain in the PGDM group was slower than that in the NC group, and the random blood glucose levels remained persistently above 16.7 mmol/L, with statistically significant differences between the two groups of SD rats(P<0.05). The birth weight, placental weight, litter size, and survival rate of offspring in the PGDM group were lower than those in the NC group(P<0.05). HE staining showed abnormal placental villous structure and uneven blood vessel thickness in the PGDM group, whereas capillaries were evenly distributed with clear edges. The protein expression of angiogenic factors, the ratios of p-PI3K/PI3K and p-AKT/AKT, and the mRNA expression levels of HIF-1 and VEGF in the PGDM group were significantly lower than those in the NC group(P<0.05). Conclusion PGDM impairs placental angiogenesis by inhibiting the PI3K/AKT signaling pathway, ultimately leading to intrauterine growth restriction in offspring. |
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