Objective To study the preliminary mechanism of estrogen therapy on estrogen deficiency-induced inju-ry of endothelium in thoracic aorta of female rats and human umbilical vein endothelial cells( HUVEC) . Methods 30 female SD rats were randomly divided into sham operation( SHAM) group,ovariectomized ( OVX) group, ovari-ectomized and estrogen treatment[ OVX+EST,0. 06 mg/( kg·d) ] group, and the treatment lasted for 6 months. HE and oil red O staining were used to observe the pathological changes of vascular endothelium. The blood vessel relaxation was analyzed by isolated vascular ring tension test. The changes of glucose regulated protein( GRP)78 and C/EBP homologous protein( CHOP) expression were examined by RT-PCR and Western blot respectively. HUVEC were divided into normal control ( CON ) group, normal +Tunicamycin control ( TM ) group, estrogen deficiency (ES-D) group, gradient concentrations of estrogen treatment(10 -9, 10 -8 and 10 -7 mol/L estradiol) group,and oxidative stress and endoplasmic reticulum stress indices were detected. Results The OVX rats showed greater weight,obvious injury and lipid depositionin in the endothelium of thoracic aorta. The OVX+EST rats showed im-proved above indices. In HUVEC cells, reactive oxygen species( ROS) were elevated and expressions of GRP78 and CHOP were increased in TM and ES-D group, different concentrations of estrodiol treatment alleviated the a-bove stress,and showed somewhat dose-dependent effect. Conclusion Estrogen deficiency cause damages of endo-thelium in thoracic aorta and HUVEC by increasing oxidative stress and endoplasmic reticulum stress, estrogen sup-plement inverts the above stress.%目的：探讨雌激素治疗对去卵巢大鼠胸主动脉内皮与雌激素缺乏的人脐静脉内皮细胞( HUVEC)的初步机制。方法将30只雌性SD大鼠随机分为假手术对照( SHAM )组、去卵巢( OVX)组、去卵巢+雌激素治疗[ OVX +EST,0．06 mg/( kg·d)雌二醇)组,6个月后观察血管内皮的病理学变化,血管环张力实验检测血管舒张差异, RT-PCR 及Western blot法分析葡萄糖调节蛋白( GRP)78、C/EBP同源蛋白( CHOP)表达的改变。将HUVEC分为正常对照( CON)组、正常+衣霉素对照( TM)组、雌激素缺乏( ES-D)组、雌激素缺乏+梯度浓度雌激素治疗(10-9、10-8、10-7 mol/L雌二醇)组,检测氧化应激及内质网应激指标的变化。结果OVX组大鼠体重增加,胸主动脉内皮出现损伤及脂质沉积, GRP78、CHOP的mRNA与蛋白表达水平上调；OVX+EST组上述指标均显著逆转。 HUVEC中ES-D组表现出活性氧簇升高及GRP78、CHOP的表达升高,补充不同浓度雌激素后上述指标均下降,且表现出一定的剂量效应。结论雌激素缺乏可介导大鼠胸主动脉内皮损伤及HUVEC出现氧化应激和内质网应激,补充雌激素后可逆转此效应。
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