中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2014年
22期
1696-1700
,共5页
袁梦琪%段争%孙彦利%袁雅冬
袁夢琪%段爭%孫彥利%袁雅鼕
원몽기%단쟁%손언리%원아동
高血压,肺性%缺氧%雌激素类%血管紧张素类%大鼠
高血壓,肺性%缺氧%雌激素類%血管緊張素類%大鼠
고혈압,폐성%결양%자격소류%혈관긴장소류%대서
Hypertension,pulmonary%Anoxia%Estrogens%Angiotensins%Rats
目的：探讨雌激素对低氧性肺动脉高压大鼠体内血管紧张素转换酶-血管紧张素Ⅱ-血管紧张素受体-1（ ACE-AngⅡ-AT1）轴的影响。方法将60只健康雌性SD大鼠按随机数字表法随机平分为6组：假手术组、单纯去势组、单纯低氧组、去势＋低氧组、去势＋雌激素组、去势＋低氧＋雌激素组。假手术组打开腹腔找到双侧卵巢后不做处理直接还纳缝合，单纯去势组行切除卵巢术，单纯低氧组持续低氧（24 h，8周），去势＋低氧组切除卵巢后持续低氧，去势＋雌激素组切除卵巢后每天给予雌激素20μg· kg -1皮下注射，去势＋低氧＋雌激素组切除卵巢后每天给予雌激素并且持续低氧。连续饲养8周，以建立低氧肺动脉高压模型。测量平均肺动脉压（ mPAP）后放血处死大鼠，观察右心室肥厚指数（ RVHI）、HE染色观察肺小动脉重塑情况。用放射免疫法、紫外分光光度法、Western印迹法、反转录PCR测定AngⅡ、ACE、AT1水平。结果单纯低氧组和去势＋低氧组大鼠肺小动脉管壁增厚管腔变窄明显， mPAP、RVHI 分别为（32.4±2.2） mmHg （1 mmHg ＝0.133 kPa ）、0.331±0.032和（37.9±1.6） mmHg、0.433±0.033，均显著高于假手术组的（12.6±1.8） mmHg、0.233±0.029（均P＜0.05）；去势＋低氧＋雌激素组上述改变较轻，mPAP[（26.1±1.4）mmHg]显著高于假手术组（P＜0.05），而RVHI （0.267±0.040）与假手术组差异无统计学意义（P＞0.05）。 ACE、AngⅡ、AT1表达水平在单纯去势组、单纯低氧组、去势＋低氧组均升高，且均显著高于假手术组（均P＜0.05），而去势＋雌激素组、去势＋低氧＋雌激素组上述指标表达水平变化不明显（均P＞0.05）。结论雌激素对低氧性肺动脉高压的干预作用可能部分是通过下调肺组织ACE和AT1受体的表达从而降低ACE-AngⅡ-AT1轴活性实现的。
目的：探討雌激素對低氧性肺動脈高壓大鼠體內血管緊張素轉換酶-血管緊張素Ⅱ-血管緊張素受體-1（ ACE-AngⅡ-AT1）軸的影響。方法將60隻健康雌性SD大鼠按隨機數字錶法隨機平分為6組：假手術組、單純去勢組、單純低氧組、去勢＋低氧組、去勢＋雌激素組、去勢＋低氧＋雌激素組。假手術組打開腹腔找到雙側卵巢後不做處理直接還納縫閤，單純去勢組行切除卵巢術，單純低氧組持續低氧（24 h，8週），去勢＋低氧組切除卵巢後持續低氧，去勢＋雌激素組切除卵巢後每天給予雌激素20μg· kg -1皮下註射，去勢＋低氧＋雌激素組切除卵巢後每天給予雌激素併且持續低氧。連續飼養8週，以建立低氧肺動脈高壓模型。測量平均肺動脈壓（ mPAP）後放血處死大鼠，觀察右心室肥厚指數（ RVHI）、HE染色觀察肺小動脈重塑情況。用放射免疫法、紫外分光光度法、Western印跡法、反轉錄PCR測定AngⅡ、ACE、AT1水平。結果單純低氧組和去勢＋低氧組大鼠肺小動脈管壁增厚管腔變窄明顯， mPAP、RVHI 分彆為（32.4±2.2） mmHg （1 mmHg ＝0.133 kPa ）、0.331±0.032和（37.9±1.6） mmHg、0.433±0.033，均顯著高于假手術組的（12.6±1.8） mmHg、0.233±0.029（均P＜0.05）；去勢＋低氧＋雌激素組上述改變較輕，mPAP[（26.1±1.4）mmHg]顯著高于假手術組（P＜0.05），而RVHI （0.267±0.040）與假手術組差異無統計學意義（P＞0.05）。 ACE、AngⅡ、AT1錶達水平在單純去勢組、單純低氧組、去勢＋低氧組均升高，且均顯著高于假手術組（均P＜0.05），而去勢＋雌激素組、去勢＋低氧＋雌激素組上述指標錶達水平變化不明顯（均P＞0.05）。結論雌激素對低氧性肺動脈高壓的榦預作用可能部分是通過下調肺組織ACE和AT1受體的錶達從而降低ACE-AngⅡ-AT1軸活性實現的。
목적：탐토자격소대저양성폐동맥고압대서체내혈관긴장소전환매-혈관긴장소Ⅱ-혈관긴장소수체-1（ ACE-AngⅡ-AT1）축적영향。방법장60지건강자성SD대서안수궤수자표법수궤평분위6조：가수술조、단순거세조、단순저양조、거세＋저양조、거세＋자격소조、거세＋저양＋자격소조。가수술조타개복강조도쌍측란소후불주처리직접환납봉합，단순거세조행절제란소술，단순저양조지속저양（24 h，8주），거세＋저양조절제란소후지속저양，거세＋자격소조절제란소후매천급여자격소20μg· kg -1피하주사，거세＋저양＋자격소조절제란소후매천급여자격소병차지속저양。련속사양8주，이건립저양폐동맥고압모형。측량평균폐동맥압（ mPAP）후방혈처사대서，관찰우심실비후지수（ RVHI）、HE염색관찰폐소동맥중소정황。용방사면역법、자외분광광도법、Western인적법、반전록PCR측정AngⅡ、ACE、AT1수평。결과단순저양조화거세＋저양조대서폐소동맥관벽증후관강변착명현， mPAP、RVHI 분별위（32.4±2.2） mmHg （1 mmHg ＝0.133 kPa ）、0.331±0.032화（37.9±1.6） mmHg、0.433±0.033，균현저고우가수술조적（12.6±1.8） mmHg、0.233±0.029（균P＜0.05）；거세＋저양＋자격소조상술개변교경，mPAP[（26.1±1.4）mmHg]현저고우가수술조（P＜0.05），이RVHI （0.267±0.040）여가수술조차이무통계학의의（P＞0.05）。 ACE、AngⅡ、AT1표체수평재단순거세조、단순저양조、거세＋저양조균승고，차균현저고우가수술조（균P＜0.05），이거세＋자격소조、거세＋저양＋자격소조상술지표표체수평변화불명현（균P＞0.05）。결론자격소대저양성폐동맥고압적간예작용가능부분시통과하조폐조직ACE화AT1수체적표체종이강저ACE-AngⅡ-AT1축활성실현적。
Objective To explore the effects of estrogen ( E2 ) on angiotensin converting enzyme-angiotensinⅡ-angiotensin type 1 receptor ( ACE-AngⅡ-AT1 ) axis in hypoxic pulmonary hypertension rats.Methods A total of 60 healthy female Sprague-Dawdley ( SD ) rats were divided randomly into 6 groups (n=10 each) of sham operation,pure ovariectomy (OVX),pure hypoxia,OVX+hypoxia,OVX+E2 and OVX+hypoxia +E2.Abdominal cavity was opened for sham operation group and bilateral ovaries were left intact without any other procedure.The pure OVX group underwent oophorectomy.The pure hypoxia group were placed into a low-oxygen environment (24 hour,8 weeks).The OVX+hypoxia group were placed into a low-oxygen environment after bilateral oophorectomy.The OVX+E2 group received a subcutaneous injection of E2 (20 μg· kg-1 · d-1 ) after bilateral oophorectomy.The OVX+hypoxia +E2 group had an injection of E2 and was placed into a low-oxygen environment after bilateral oophorectomy.The rats were feed continuously for 8 weeks to establish hypoxic pulmonary hypertension model.The mean pulmonary artery pressure ( mPAP ) was measured after bloodletting.Then right ventricle hypertrophy index ( RVHI ) and hematoxylin-eosin pulmonary artery remodeling ( HPSR ) were observed.And electron microscope was employed to observe pulmonary arteriolar ultrastructure.The methods of radio-immunity assay , ultraviolet spectroscopy,Western blot and reverse transcription PCR were used to measure the levels of CE ,AngⅡand AT1 in sera,lung and pulmonary artery.Results The vascular walls of pure hypoxia and OVX +hypoxia groups became thickened and lumen narrowed.mPAP and RVHI were ( 32.4 ±2.2 ) mmHg ( 1 mmHg=0.133 kPa),0.331 ±0.032 and (37.9 ±1.6) mmHg,0.433 ±0.033.Both were significantly higher than those of Sham operation group ( ( 12.6 ±1.8 ) mmHg, 0.233 ±0.029 ) ( both P <0.05 ); the above parameters of OVX +Hypoxia +E2 group changed little.And mPAP ( ( 26.1 ±1.4 ) mmHg ) was significantly higher than that in sham operation group ( P<0.05 ) while the difference in RVHI between OVX+Hypoxia +E2 ( 0.267 ±0.040 ) and sham operation groups had no statistical significance ( P>0.05).Compared with Sham operation group ,the expression levels of ACE ,AngⅡ and AT1 in pure OVX, pure hypoxia and OVX+hypoxia groups rose markedly (all P<0.05).However,the OVX+E2 and OVX+hypoxia+E2 groups had no obvious change (all P>0.05).Conclusion The intervention effect of E2 for hypoxic pulmonary hypertension may be partly mediated by the down-regulated expressions of ACE and AT 1 in lung tissue resulting in the reduced activity of ACE-AngⅡ-AT1 axis.
