低氧诱导大鼠肺动脉中5-HT_(1B)受体的过度表达  

Hypoxia induces overexpression of 5-HT_(1B) receptor in rat pulmonary arteries

作　　者：王佳兴[1] 唐发宽[1] 肖军[1] 华宁[1] 布伦[1] 张玉顺[2] 朱妙章[3] 

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 [3]第四军医大学生理学教研室,陕西西安710032

出　　处：《心脏杂志》2010年第6期842-845,共4页Chinese Heart Journal

摘　　要：目的:观察低氧对大鼠肺动脉中5-羟色胺1B(5-HT1B)受体表达的影响,初步探讨了5-HT1B受体在低氧性肺动脉高压形成中的变化。方法:40只健康雄性SD大鼠随机分为正常组、低氧3周组、低氧4周组和低氧6周组,每组10只。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6周。测定各组大鼠的平均肺动脉压力(mPAP)、右心室收缩压(RVSP)和右心室肥厚度。应用免疫组化染色法检测大鼠肺动脉上5-HT1B的分布和表达;用Western blot法测定大鼠肺组织中5-HT1B受体蛋白的含量。结果:与正常组相比,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)。免疫组化染色的结果显示,5-HT1B受体主要分布在正常大鼠肺动脉的内膜层,平滑肌肌层中仅有少量表达;与正常组相比,低氧3周组大鼠肺动脉平滑肌肌层中5-HT1B受体的表达显著增多(P<0.05);随着低氧时间的延长,表达持续增多。Western blot的结果表明,大鼠肺组织中5-HT1B受体蛋白含量的变化与免疫组化染色法检测的结果相一致。结论:低氧可以诱导大鼠肺动脉中5-HT1B受体的过度表达,这可能是5-羟色胺系统参与低氧性肺动脉高压形成的机制之一。AIM ： To investigate the effects of hypoxia on the expressions of 5-HT1B receptors in rat pul- monary arteries and to explore the mechanism of hypoxic pulmonary hypertension （HPH）. METHODS ： Forty male Sprague Dawley rats were randomly divided into four groups： normoxia control, 3-week hypoxia, 4-week hypoxia and 6-week hypoxia. The rats in normoxia control remained in a normal environment, whereas rats in 3- , 4- and 6-week hypoxia groups were kept, respectively, in hypoxia chamber for 3, 4 and 6 weeks to establish the HPH animal model. After HPH rats were established, mean pulmonary pressure （mPAP） and right ventricular systolic pressure （RVSP） were recorded by a mierocatheter. RV/（ LV ＋ S） ratio was calculated to assess fight ventricular hypertrophy. 5-HTIB receptor expressions in pulmonary arteries and lung tissues were measured by immunohistoehemistry and Western blot analyses. RESULTS： Compared with those in normoxia control group, mPAP, RVSP and RV/（LV ＋ S）% of 3-week hypoxia rats increased significantly （P 〈 0. 05）, which continued to increase following prolonged hypoxia. Immunohistochemistry showed that 5-HT1B was localized mainly in the intima of pulmonary arteries of normoxia group of rats. Exposed to hypoxia, 5-HTIB receptor increased in the media of rat pulmonary arteries, particularly those bordering the adventitia. More changes were observed in the expressions of 5-HTI~ receptor following prolonged hypoxia. Western blot results showed the same changes of 5-HTIR receptor expressions in lung tissues as that of 5-HTIB receptor immunoreactivity in pulmonary arteries. CONCLUSION ： Hypoxia induces overexpression of 5-HTlB receptor in pulmonary arteries of HPH rats, which may be one of the underlying mechanisms of 5-HT-induced HPH development.

关 键 词：低氧 肺动脉高压 5-羟色胺 5-羟色胺受体 大鼠 

分 类 号：R543.2[医药卫生—心血管疾病]