| 沈毅,章琪滢,傅萍.寿胎丸调节PI3K/AKT信号通路促进DEHP暴露孕鼠母胎界面血管生成[J].浙江中西医结合杂志,2025,35(7): |
| 寿胎丸调节PI3K/AKT信号通路促进DEHP暴露孕鼠母胎界面血管生成 |
| Shoutai Pills promotes angiogenesis at the maternal-fetal interface in DEHP-exposed pregnant rats by regulating PI3K/AKT signaling pathway |
| 投稿时间:2024-11-19 修订日期:2025-03-21 |
| DOI: |
| 中文关键词: 寿胎丸 DEHP 母胎界面 血管生成 PI3K/AKT信号通路 HIF-1α VEGF |
| 英文关键词:Shoutai Pills DEHP Maternal-fetal interface Angiogenesis PI3K/AKT signaling pathway HIF-1α VEGF |
| 基金项目:浙江省中医药科技计划项目(No.2023ZR113) |
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| 中文摘要: |
| 目的 研究寿胎丸对邻苯二甲酸二乙酯(DEHP)暴露孕鼠母胎界面血管生成的调节作用及机制。方法 将48只雌性SD大鼠随机分为正常组、模型组、黄体酮胶囊组、寿胎丸组,按雌雄比例2∶1合笼建立妊娠模型,于妊娠第1日开始,分别予正常组玉米油10 mL/kg+生理盐水10 mL/kg、模型组DEHP 500 mg/kg+生理盐水10 mL/kg、黄体酮胶囊组DEHP 500 mg/kg+黄体酮胶囊150 mg/kg、寿胎丸组DEHP 500 mg/kg+寿胎丸44 g/kg灌胃至妊娠19日;观察各组大鼠的胚胎丢失情况,通过苏木素-伊红染色法观察胎盘组织血管数量及形态,免疫组织化学法、实时荧光定量PCR技术观察大鼠胎盘组织磷脂酰肌醇-3激酶(PI3K)、蛋白激酶B(AKT)、缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)蛋白及mRNA表达。结果 与正常组比较,模型组大鼠胚胎丢失率[(19.37±9.57)%比(6.68±5.08)%,P<0.01]升高,胎盘组织迷路带血管数量明显减少,管腔狭窄,血管壁不完整,胎盘组织中PI3K[(0.15±0.01)比(0.24±0.03),P<0.01]、AKT[(0.13±0.02)比(0.27±0.02),P<0.01]、HIF-1α[(0.16±0.02)比(0.27±0.01),P<0.01]、VEGF[(0.17±0.01)比(0.30±0.03),P<0.01]蛋白表达降低,胎盘组织中PI3K[(0.42±0.12)比(1.01±0.01),P<0.01]、AKT[(0.25±0.08)比(1.01±0.01),P<0.01]、HIF-1α[(0.24±0.11)比(1.01±0.01),P<0.01]、VEGF[(0.21±0.05)比(1.01±0.01),P<0.01]mRNA的表达下降。与模型组比较,寿胎丸组大鼠胚胎丢失率[(7.71±5.92)%比(19.37±9.57)%,P<0.01]降低,胎盘组织迷路带血管数量明显增多,管腔充盈且管壁完整,胎盘组织中PI3K[(0.25±0.02)比(0.15±0.01),P<0.01]、AKT[(0.25±0.02)比(0.13±0.02),P<0.01]、HIF-1α[(0.26±0.02)比(0.16±0.02),P<0.01]、VEGF[(0.27±0.02)比(0.17±0.01),P<0.01]蛋白表达升高,胎盘组织中PI3K[(0.86±0.07)比(0.42±0.12),P<0.01]、AKT[(0.66±0.10)比(0.25±0.08),P<0.01]、HIF-1α[(0.73±0.15)比(0.24±0.11),P<0.01]、VEGF[(1.05±0.18)比(0.21±0.05),P<0.01]mRNA的表达上升。结论 寿胎丸可能通过调控PI3K/AKT信号通路,上调HIF-1α和VEGF表达,促进母胎界面血管生成,从而降低胚胎丢失率,改善妊娠结局。 |
| 英文摘要: |
| Objective To investigate the effect and mechanism of Shoutai pills on angiogenesis at the maternal-fetal interface in pregnant rats exposed to di-2-ethyl hexylphthalate(DEHP). Methods Forty-eight female Sprague-Dawley rats were randomly divided into normal group, model group, progesterone capsule group and Shoutai pills group. The pregnancy model was established by mating the male to female ratio of 2:1. From the first day of pregnancy, the rats in the normal group were treated with 10 mL/kg corn oil and 10 mL/kg normal saline, the rats in the model group were treated with 500 mg/kg DEHP and 10 mL/kg normal saline, the rats in the progesterone capsule group were treated with 500 mg/kg DEHP and 150 mg/kg progesterone capsule, and the rats in the Shoutai pills group were treated with 500 mg/kg DEHP+ Shoutai pills 44 g/kg by gavage until the 19th day of pregnancy. The embryo loss of rats in each group was observed. The number and morphology of placental blood vessels were observed by hematoxylin-eosin staining. The expression of phosphatidylinositol-3 kinase(PI3K), protein kinase B(AKT), hypoxia-inducible factor-1α( HIF-1α), vascular endothelial growth factor(VEGF) protein and mRNA in rat placental tissue were observed by immunohistochemistry and real-time fluorescence quantitative PCR. Results Compared with the normal group, the embryo loss rate of rats in the model group was increased[(19.37±9.57)% vs. (6.68±5.08)%,P<0.01], the number of blood vessels in the labyrinth zone of placenta was significantly reduced, the vascular lumen was narrow, the blood vessel wall was incomplete, the protein expressions of PI3K[(0.15±0.01) vs. (0.24±0.03),P<0.01], AKT[(0.13±0.02) vs. (0.27±0.02),P<0.01], HIF-1α[(0.16±0.02) vs. (0.27±0.01),P<0.01], and VEGF[(0.17±0.01) vs. (0.30±0.03),P<0.01] in placental tissue were decreased, the mRNA expressions of PI3K[(0.42±0.12) vs. (1.01±0.01),P<0.01], AKT[(0.25±0.08) vs. (1.01±0.01),P<0.01], HIF-1α[(0.24±0.11) vs. (1.01±0.01),P<0.01], and VEGF[(0.21±0.05) vs. (1.01±0.01),P<0.01] in placental tissue were decreased. Compared with the model group, the embryo loss rate of rats in the Shoutai pills group was decreased[(7.71±5.92)% vs. (19.37±9.57)%,P<0.01], the number of blood vessels in the labyrinth zone of placenta was significantly increased, the vascular lumen was full and the blood vessel wall was intact, the protein expressions of PI3K[(0.25±0.02) vs. (0.15±0.01),P<0.01], AKT[(0.25±0.02) vs. (0.13±0.02),P<0.01], HIF-1α[(0.26±0.02) vs. (0.16±0.02),P<0.01] and VEGF[(0.27±0.02) vs. (0.17±0.01),P<0.01] in placental tissue were increased, the mRNA expressions of PI3K[(0.86±0.07) vs. (0.42±0.12),P<0.01], AKT[(0.66±0.10) vs. (0.25±0.08),P<0.01], HIF-1α[(0.73±0.15) vs. (0.24±0.11),P<0.01] and VEGF[(1.05±0.18) vs. (0.21±0.05),P<0.01] in placental tissue were increased. Conclusion Shoutai Pills can reduce embryo loss rate and improve pregnancy outcome by regulating PI3K/AKT signaling pathway, up-regulating HIF-1α and VEGF expression, and promoting angiogenesis at the maternal-fetal interface. |
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