雌激素及其受体对低氧性肺血管重建的作用

Effect of estrogen and its receptor on the hypoxic pulmonary vascular remodeling

目的:探讨雌激素及其受体对低氧性肺血管重建的作用。方法:采用间断常压低氧法建立大鼠低氧性肺动脉高压模型。将30只雄性SD大鼠随机分成:对照组、雌激素预防组、低氧组、雌激素治疗组、治疗对照组。以右心导管法测定平均肺动脉压(mPAP);测定右心室肥厚指数[RV/(LV+S)];图像分析技术测定肺小血管管壁厚度;用放射免疫法测定血清17-β雌二醇浓度。用RT-PCR方法检测肺组织中ERβmRNA的表达,用免疫组化染色法检测肺小血管壁的ERβ蛋白表达。结果:①低氧组、治疗对照组大鼠mPAP、RV/(LV+S)、WT%和WA%均高于对照组;雌激素预防组、雌激素治疗组大鼠mPAP、RV/(LV+S)、WT%和WA%均低于低氧组、治疗对照组。②低氧组、治疗对照组大鼠ERβmRNA表达量和ERβ蛋白表达与正常对照组无差异。经雌激素干预后,雌激素预防组、雌激素治疗组的ERβmRNA表达和ERβ蛋白表达显著高于低氧组、治疗对照组。结论:17-β雌二醇能有效降低低氧性肺动脉高压大鼠的肺动脉压力、阻抑右心室肥厚,对低氧性肺动脉高压血管重建具有一定的预防和治疗作用,其作用可能是通过雌激素受体β实现的。

AIM： To observe the effect of estrogen and its receptor on the hypoxic pulmonary vascular remodeling.METHODS： The animal model of hypoxic pulmonary hypertension was established by exposing the rats to normabaric hypoxic conditions for 3 weeks. Thirty male SD rats were randomly divided into five groups： control group, E2 preventive group, hypoxia group, E2 treatment group and E2 treatment control group. The mean pulmonary artery pressure （mPAP） was examined by right cardiac catheterization, and the RV/（ LV ＋ S） was calculated. The lung specimens were examined by light microscope and morphological analysis semiquantitatively. E2 in serum was measured by means of the radioimmunoassay. The expression of ERβ mRNA in lung tissues was detected by reverse transcription - polymerase chain reaction （ RT -PCR）, ERβ protein in pulmonary small vessels was detected by immunohistochemistry. RESULTS： ① In hypoxia group and E2 treatment control group, mPAP, the RV/（LV ＋S）, WT% and WA% increased significantly compared with those in control group, respectively. In the preventive and treatment group, the mPAP, the RV/（ LV ＋ S）, WT% and WA% decreased remarkably as compared with those in their control group, respectively. ② In hypoxia group and E2 treatment control group, the expression of ERβmRNA and ERβ protein were not signilicantly different from that in control rats. In hypoxia group and E2 treatment control group, the expression of ERβ mRNA and ERβ protein were higher than that in their control group, respectively. CONCLUSION： E2 has protective effects on the hypoxic pulmonary remodeling through increasing the expression of ERβ in the lung and pulmonary small vessels in HPH rats.