铅致胎盘损伤机制的研究进展(英文)

The Underlying Mechanism of Lead-induced Placental Injury

铅是一种嗜神经和嗜胎盘的毒性重金属,本综述主要是关于铅的胎盘毒性。孕期铅暴露可以导致胎盘重量减轻,滋养层增生,血管堵塞,细胞间隙增宽,血管周围大量的纤维蛋白沉积,以及粗面内质网扩张,膜上核糖体数量减少。当孕期铅暴露在一定范围内时,一氧化氮(NO),一氧化氮合酶(NOS)水平升高,以保证胎盘组织器官的正常结构和功能;进一步加重时,NO及NOS反而降低,导致胎儿-胎盘循环阻力增高,胎盘灌注量下降;孕期铅暴露时,丙二醛(MDA)升高,说明存在胎盘氧化与抗氧化系统平衡失调;基质金属蛋白酶-9(MMP-9)表达降低,而基质蛋白酶组织抑制因子-1(TIMP-1)表达增强,胎盘MMP-9/TIMP-1的表达失衡,导致滋养细胞浸润能力减弱,胎盘着床过浅,血管重铸障碍,从而影响胎盘发育及胎儿生长;染铅胎盘NF-kB的表达及血栓调节蛋白(TM)的表达明显高于对照组。NF-kB的激活又可以反式激活表皮生长因子,血小板生长因子等的表达,促进血管平滑肌细胞的增殖,细小动脉胶原纤维增加,血管痉挛性收缩;TM表达异常,说明孕期铅暴露可致胎盘血管内皮细胞损伤。总之,孕期铅暴露可引起胎盘病理及一系列的分子化学改变,从而影响胎盘功能和胎儿发育,可引起子代早产、出生体重低、智力障碍等。

Lead （Pb＋） is a toxic heavy metal with high affinity to neurons and placenta. This review mainly focused on the lead placental toxicity. Placental lead exposure in rats leads to placenta weight loss, trophoblast hyperplasia, vascular congestion, increase of intracellular spaces and deposits of hyaline material of perivascular predominance, accompanied with the distention of rough endoplasmic reticula and reduction of the ribosomal number on membranes. All pathological presentations are consistent with molecular chemistry changes. NO and NOS levels were significantly higher in rats with lead exposure. However, extensive period of lead exposure may de- compensate the host regulation, subsequently increase fetal-placental vascular resistance, leading to decrease in placental perfusion and then fetal hypoxia-ischemia; MDA level was significantly higher in the placenta of lead exposed than the control group （P〈0.05）. Thus, it is believed that imbalance of oxidation and antioxidant in placenta following lead exposure contributed to placenta damage. The expres- sion of MMP-9 in the placentas was significantly higher in the lead exposed group than the control. We also found the positive correlation between lead poisoning and the expression of TIMP-1 on placental trophoblasts, suggesting that lead exposure during pregnancy causes imbalance of MMP-9/TIMP-1 expression, and subsequently resulting in reduced trophoblast invasion, shallow implantation, vascular re- modeling barriers. The expression of nuclear factor NF-KB and thrombomodulin were significantly higher in the lead exposed placen- ta. than the controls. The activation of NF-κB can trans-activate the epidermal growth factor, platelet derived growth factor expression, and promote smooth muscle cell proliferation, vascular remodeling in membrane signal transduction, thereby increase the thickness of the collagen fibers of small arteries and vascular wall, enhance vascular spasm contraction, increase mean arterial pressure, and finally result in pregnancy hypertension. The abnormal, expression of thrombomodulin suggests lead exposure during pregnancy causing placental vas- cular endothelial injury, causes placental vascular endothelial injury. In a word, lead exposure during pregnancy causes pathological pre- sentations and molecular chemistry changes. Thus may lead to premature birth, low birth weight, and mental retardation.