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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。
OBJECTIVE: To observe the effect of hypoxia on the expression of 5-HT1B receptor in rat pulmonary artery and to explore the change of 5-HT1B receptor in hypoxic pulmonary hypertension. Methods: Forty healthy male SD rats were randomly divided into normal group, hypoxia 3 weeks group, hypoxia 4 weeks group and hypoxia 6 weeks group, 10 rats in each group. Except normal group, the other three groups were housed in hypoxic environment for 3 weeks, 4 weeks and 6 weeks respectively. The mean pulmonary arterial pressure (mPAP), right ventricular systolic pressure (RVSP) and right ventricular hypertrophy were measured in each group. The distribution and expression of 5-HT1B in rat pulmonary artery were detected by immunohistochemical staining. The content of 5-HT1B receptor protein in rat lung tissue was determined by Western blot. Results: Compared with the normal group, mPAP, RVSP and right ventricular hypertrophy were significantly increased (all P <0.05) in hypoxia 3 weeks group, and continued to increase with hypoxia time (all P <0.05). The results of immunohistochemical staining showed that the 5-HT1B receptor mainly distributed in the intima of pulmonary artery of normal rats, and only a small amount was expressed in the smooth muscle. Compared with the normal group, the pulmonary arterial smooth muscle The expression of 5-HT1B receptor in the layer was significantly increased (P <0.05). With the prolongation of hypoxia time, the expression continued to increase. The results of Western blot showed that the change of 5-HT1B receptor protein content in lung tissue of rats was consistent with the results of immunohistochemical staining. CONCLUSION: Hypoxia induces overexpression of 5-HT1B receptor in pulmonary arteries of rats, which may be one of the mechanisms involved in the formation of hypoxic pulmonary hypertension.