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Title:: Hypoxia induces overexpression of 5-HT1B 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; 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）

Author(s):: WANG Jia-xing1; TANG Fa-kuan1; XIAO Jun1; HUA Ning1; BU Lun1; ZHANG Yu-shun2; ZHU Miao-zhang3; 1.Department of Cardiology, PLA 309th Hospital, Beijing 10091, China; 2.Second Department of Cardiology, First Affiliated Hospital, Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China; 3.Department of Physiology, School of Basic Medicine, Fourth Military Medical University, Xi’an 710032, Shaanxi, China

关键词:: 低氧; 肺动脉高压; 5-羟色胺; 5-羟色胺受体; 大鼠

Keywords:: hypoxia; pulmonary hypertension; serotonin; serotonin receptor; rat

分类号:: R543.2

DOI:: -

文献标识码:: A

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。

Abstract:: AIM: To investigate the effects of hypoxia on the expressions of 5-HT1B receptors in rat pulmonary 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 microcatheter. RV/(LV+S) ratio was calculated to assess right ventricular hypertrophy. 5-HT1B receptor expressions in pulmonary arteries and lung tissues were measured by immunohistochemistry 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-HT1B receptor increased in the media of rat pulmonary arteries, particularly those bordering the adventitia. More changes were observed in the expressions of 5-HT1B receptor following prolonged hypoxia. Western blot results showed the same changes of 5-HT1B receptor expressions in lung tissues as that of 5-HT1B receptor immunoreactivity in pulmonary arteries. CONCLUSION: Hypoxia induces overexpression of 5-HT1B receptor in pulmonary arteries of HPH rats, which may be one of the underlying mechanisms of 5-HT-induced HPH development.

参考文献/References

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低氧诱导大鼠肺动脉中5-HT1B受体的过度表达

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

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