野百合碱诱导的肺动脉高压大鼠肺血管5-HT转载体表达增强

Increased expression of 5-hydroxytryptamine transporter gene in monocrotaline-induced pulmonary hypertension in rats

目的 研究野百合碱诱导的大鼠肺动脉高压与5 HT转载体基因表达的关系。方法 应用MCT诱导的慢性肺动脉高压大鼠模型,建立离体动脉环5 HT浓度反应曲线;HE染色观察肺动脉构型重建,应用RT PCR检测大鼠肺动脉5 HT转载体mRNA表达。结果 MCT大鼠肺血管对5 HT收缩反应增强,肺肌型小动脉中膜增厚,MCT诱导的肺动脉高压大鼠肺血管5 HT转载体mRNA表达明显增多。5 HT转载体基因表达与肺肌型小动脉中膜增厚有明显相关性。结论 MCT诱导的肺动脉高压大鼠肺血管构型重建及5 HT引起收缩反应增强,伴有5 HT转载体mRNA表达增多;同时5 HT转载体mRNA表达与肺肌型小动脉中膜增厚有明显相关性,提示5 HT转载体可能在肺动脉高压中起重要作用。

Aim To study the relationship between pul-monary hypertension (PHT) and 5-hydroxytrapta-mine transporter (5-HTT) in the pulmonary arteries (PAs) from normal and monocrotaline (MCT) induced pulmonary hypertension rats. Methods MCT-treated rats were used as a model for chronic PHT.Concentration-response curves of 5-hydroxytraptamine induced pulmonary vasoconstriction were established. The medial wall thickness of pulmonary arteries was measured. Semi-quantitative RT-PCR was performed to identify the expression of 5-HTT mRNA in rat PAs.Results 5-HT induced vasoconstriction response of PAs from MCT rats was significantly increased.The thickness of pulmonary vascular medial walls was increased in MCT rats. A significantly higher level of 5-HTT mRNA expression was detected in PAs from MCT rats. The ratio of the PCR products of 5-HTT gene to those of β-actin gene was higher in MCT rats than in control rats. 5-HTT mRNA expression of pulmonary arteries correlated with the thickness of pulmonary vascular medial walls in rats.Conclusions MCT-induced pulmonary vascular remodeling and increased vascular contractile response to 5-HT were accompanied with enhanced level of 5-HTT mRNA expression and there existed correlation between the wall thickness of pulmonary arteries and 5-HTT mRNA expression,indicating 5-HTT is an important mechanism involved in pulmonary hypertension.