目的探讨胎儿宫内慢性缺氧对子代成年期血管内皮功能的影响及其与性别、高脂血症和再缺氧的关系。方法采用四因素两水平析因设计,研究宫内慢性缺氧、性别、高脂血症、成年期再缺氧对血管内皮依赖性舒张功能的影响。建立大鼠宫内慢性缺氧模型、高脂血症模型与成年期再缺氧模型,观测大鼠血管内皮依赖性舒张功能以及动脉内皮形态学改变。结果除性别因素外,宫内缺氧、高脂血症和再缺氧三个因素均可引起内皮依赖性舒张功能减退(均P〈0.01),其主效应分别为14.1%、14.2%和12.9%,其中宫内缺氧与高脂血症对血管内皮功能的影响存在协同交互作用(F=4.889,P〈0.05),其余因素之间不存在显著性交互作用。宫内缺氧组部分内皮细胞水肿、坏死、甚至脱落,局部血小板堆积微血栓形成,内皮下层水肿,偶见炎症细胞浸润;正常对照组动脉内皮细胞层结构完整,未见上述改变。结论慢性宫内缺氧可引起子代成年期血管内皮功能与结构的损害,其作用强度与高脂血症、成年期缺氧相近,且可与高脂血症协同促进血管内皮损伤。
Aim To investigate the effects of fetal intrauterine chromic hypoxia on the vascular endothelial function of adult offspring rats,and its relation to gender,hyperlipemia,and adult hypoxia. Methods Four factorial experiment was designed to explore the role of fetal intrauterine chromic hypoxia,gender,hyperlipemia,and adult hypoxia on endothelial dependent diastolic function.Four animal models of intrauterine chromic hypoxia,hyperlipemia and adult hypoxia were established in Sprague-Dawley rats.Endothelial dependent diastolic function and histologic changes were determined in the rats offsping. Results Except the factor of gender,the other three factors of intrauterine hypoxia,hyperlipemia,and adult hypoxia resulted in an impairment of endothelial dependent diastolic function with main effects of 14.1%,14.2%,12.9%,respectively(all P〈0.01).There was a positive interaction between intrauterine hypoxia and hyperlipemia on endothelial function(F=4.889,P〈0.05),but no other significant interactions among these four factors.Furthermore,marked histological changes,such as edema,necrosis,and desquamation of vascular epithelium,platelet aggregation and microthrombosis,subendothelial edema and infiltration of inflammatory cells,were observed in the fetal hypoxia offspring but not in the control group. Conclusion Intrauterine chromic hypoxia can induce both functional and morphologic impairment in vascular endothelium from adult offspring rats.This effect on the impaired endothelial function was similar to hyperlipemia and adult hypoxia on that,and was enhanced with hyperlipemia.