妊娠期大鼠镉暴露与妊娠高血压疾病的关系

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摘要目的：通过镉诱导妊娠期大鼠妊娠高血压疾病，分析镉对妊娠高血压疾病大鼠发病的毒理作用。方法：将妊娠SD大鼠随机分成3组：0.25 mg/kg镉处理组、0.5 mg/kg镉处理组和对照组，分别于妊娠第4天至第19天每天腹腔注射不同浓度的氯化镉（0.25、0.5 mg/kg）和2 mL/kg 0.9%氯化钠溶液。非孕组以0.5 mg/kg的剂量腹腔注射镉并持续相同的时间做对照。用BP-98A血压仪测量大鼠血压的变化并测量24 h尿蛋白水平。采用HE染色观察胎盘、肾脏、肝脏、脑的病理变化，并用透射电镜观察胎盘滋养细胞的超微结构。结果：0.5 mg/kg镉处理组大鼠于妊娠第12天开始血压逐渐升高，在妊娠第12天及第19天血压高于对照组及非孕组（P＜0.05），妊娠第19天0.5mg/kg镉处理组24 h尿蛋白水平也高于其余3组（P＜0.01）。HE染色结果显示，镉引起的病理改变包括胎盘绒毛血管充血、迷路区血管间膜增厚以及绒毛间纤维蛋白黏附；肾小球内皮细胞变性和肾小动脉增厚；肝及脑神经细胞水肿变性；脑灶区出血。电镜下可见胎盘滋养细胞绒毛突起减少甚至缺失，线粒体肿胀和粗面内质网脱颗粒。结论：本研究成功用镉诱发孕鼠出现高血压及蛋白尿等妊娠高血压疾病临床症状，对胎盘和肾脏等脏器造成相应病理损伤，初步表明了镉对孕期的生殖毒性效应及特点。

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	王繁
	邱海凡
	刘奕
	陈璐璐
	范风云
	王宗敏

关键词 ：妊娠高血压疾病, 镉, 胎盘滋养细胞, 病理学, 大鼠

Abstract：Objective: To explore the cadmium’s toxicological effect on development of pregnancy-related hypertensive disorders through cadmium exposure during pregnancy in rats. Methods: Pregnant SD rats were divided into three groups (0.25 mg/kg group, 0.5 mg/kg group and control group) given intraperitoneal injection of different dose of cadmium chilorde (0.25, 0.5 mg/kg) and saline every day from gestational day (GD) 4 to 19. Non-pregnant rats received an intraperitoneal injection of 0.5 mg/kg cadmium chilorde as non-pregnant controls. The effect of cadmium on systolic blood pressure was measured by BP-98A blood pressure meter. And the effect of cadmium on urinary albumin excretion was investigated by BCA protein assay kit. This study also investigated the morphological changes in placenta, kidneys, liver, brain by HE staining, and ultrastructure of placental trophoblast cells were observed with transmission electron microscopy in pregnant rat exposed to cadmium. Results: The systolic blood pressures of rats at 12 and 19 days of pregnancy was significantly elevated after injection of cadmium at dose of 0.5 mg/kg compared with that in control group and non-pregnant group at the same dose (P<0.05). The urinary albumin excretion of rats in 0.5 mg/kg group was significantly higher compared with that in other three groups at gestational day 19 (P<0.01). The morphological changes in placenta induced by cadmium included thickening of the media vessel walls, degeneration and excessive perivillous fibrin depositionin placental labyrinth. The swelling of the glomerular endothelia cells and thickening of the media renal vessel walls also were observed in kidney. Reduced placental trophoblast intracellular organelles and papilla were revealed by electron microscope. Conclusion: The key features of pregnancy-related hypertension can be observed in rat after injection with a relatively low concentration of cadmium. Through further evaluation of the reproductive toxicological characteristics of cadmium during pregnancy, it is found that cadmium induces pathological damage in the placenta, kidney, liver, and brain of rats, which is similar to pregnancy-related hypertension in human in pathophysiological aspects.

Key words： pregnancy-related hypertension cadmium placental trophoblast cells pathology rats

收稿日期: 2018-03-12

基金资助:国家自然科学基金青年基金资助项目（81501280）；浙江省自然科学基金资助项目（LY15H040012）；温州市科技计划项目（Y20150048）；浙江省科技厅科研基金资助项目（2018260097）。

作者简介: 王繁（1975-），女，浙江温州人，副教授，副主任医师，博士。

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https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2018/V48/I11/781

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