低氧性肺动脉高压大鼠肺内5-HT_(1B)受体的分布和表达变化  

Expression and distribution of 5-HT_(1B) receptors in lung tissue in rats with hypoxic pulmonary hypertension

作　　者：王佳兴[1] 唐发宽[1] 肖军[1] 华宁[1] 布伦[1] 王德水[1] 王洪叶[1] 张玉顺[2] 

机构地区：[1]解放军第309医院心内科,北京100091 [2]西安交通大学第一附属医院心内二科,陕西西安710061

出　　处：《中国病理生理杂志》2010年第8期1579-1583,共5页Chinese Journal of Pathophysiology

摘　　要：目的:观察低氧性肺动脉高压(HPH)大鼠体内5-羟色胺(5-HT)水平及其肺内5-羟色胺1B(5-HT1B)受体的分布和表达变化,探讨低氧性肺动脉高压的形成机制。方法:40只健康雄性SD大鼠随机分为正常组(control)、低氧3周组、低氧4周组和低氧5周组。除正常组外,其余3组大鼠分别在低氧环境中饲养3周、4周和5周。测定各组大鼠的平均肺动脉压力(mPAP)、右心室收缩压(RVSP)、右心室肥厚度[RV/(LV+S)%]、血浆和肺组织中5-HT含量。应用免疫组织化学法观察大鼠肺组织中5-HT1B受体的分布和表达,Western blotting法测定大鼠肺组织中5-HT1B受体的蛋白含量。结果:和正常组相比,低氧3周组大鼠的mPAP、RVSP和右心室肥厚度均显著升高(均P<0.05),并且随着低氧时间的延长而持续升高(均P<0.05)。低氧大鼠血浆和肺组织中5-HT的含量均显著高于正常组大鼠(均P<0.05),并随着低氧时间的延长而持续升高(均P<0.05)。免疫组织化学结果显示:5-HT1B受体主要分布在正常大鼠肺动脉的内膜层,而平滑肌层中仅有少量表达;和正常组相比,低氧3周组大鼠肺动脉平滑肌层中5-HT1B受体的表达显著增多;随着低氧时间的延长,大鼠肺动脉平滑肌层中5-HT1B受体表达持续增多。Western blotting结果表明,大鼠肺组织中5-HT1B受体的蛋白含量变化和免疫组织化学结果相一致。结论:低氧性肺动脉高压大鼠体内5-HT水平显著升高,其肺动脉中5-HT1B受体呈过度表达,这可能是低氧性肺动脉高压形成的分子机制之一。AIM： To investigate the changes of 5-hydroxytryptamine（5-HT）levels and to observe the expression and distribution of 5-HT1B receptors in the lung tissues of hypoxic pulmonary hypertension（HPH） rats for exploring the mechanisms of hypoxic pulmonary hypertension.METHODS： Forty male Sprague-Dawley rats were randomly divided into 4 groups： normoxia control（control group）,3 weeks hypoxia group,4 weeks hypoxia group and 5 weeks hypoxia group.The rats in normoxia control group stayed in normal environment.The rats in 3 weeks hypoxia group,4 weeks hypoxia group and 5 weeks hypoxia group were kept respectively in hypoxia chamber for 3 weeks,4 weeks and 5 weeks respectively to establish the HPH animal model.After HPH was established,the mean pulmonary pressure（mPAP） and the right ventricular systolic pressure（RVSP） were recorded by a micro-catheter.RV/（LV＋S） ratio was calculated to assess the right ventricular hypertrophy.5-HT levels in plasma and lung tissues of HPH rats were measured by ELISA.The expression and distribution of 5-HT1B receptors in the lung tissues were measured by the methods of immunohistochemistry and Western blotting.RESULTS： Compared to the normoxia controls,mPAP,RVSP and RV/（LV＋S）% in 3 weeks hypoxic rats increased significantly（P0.05）,and continued to increase following prolonged hypoxia.The results of ELISA showed that 5-HT levels in plasma and lung tissues of HPH rats continued to increase following prolonged hypoxic exposure（P0.05）.The 5-HT1B receptors were localized mainly in the intima of the pulmonary arteries in normal rats.Exposed to hypoxia,the immuno-reactivity for 5-HT1B receptors increased in the media of pulmonary arteries in 3 weeks hypoxic rats,particularly those bordering the adventitia.The increase in the expression of 5-HT1B receptor was observed following prolonged hypoxic exposure.The results of Western blotting showed the same changes of 5-HT1B receptor expression in the lung tissues as that of 5-HT1B immuno-reactivity in pulmonary

关 键 词：低氧 肺动脉高压 5-羟色胺 受体 5-羟色胺 

分 类 号：R541.4[医药卫生—心血管疾病]