4-PBA对大鼠肺动脉高压的作用及药理机制

The effect and pharmacological mechanism of 4-PBA on pulmonary hypertension in rats

为探讨4-苯基丁酸(4-PBA)对大鼠肺动脉高压的作用及机制,选取SD大鼠60只,将大鼠随机分为对照组、模型组、4-PBA组,对照组、模型组给予等量生理盐水,4-PBA组分别给予250 mg/kg或500 mg/kg 4-PBA,连续4周,观察各组大鼠血流动力学(RVSP、mPAP、PASP)、右心室重构指数(RVHI)及肺血管壁厚占血管外径的百分比(MVT%)指标,采用Western blot检测蛋白表达,结果显示,与对照组比较,模型组RVSP、mPAP、PASP、RVHI、MVT等均显著升高,α-SMA、Bcl-2和Bax等蛋白表达均显著增加,给予4-PBA干预后,上述指标和蛋白表达显著下降。结果得出4-PBA可改善肺动脉高压大鼠血流动力学、右室和肺血管重构,可能与其下调α-SMA、Bcl-2和Bax蛋白表达有关。

To investigate the effect and mechanism of 4-phenylbutyric acid(4-PBA)on pulmonary hypertension in rats,60 SD rats were randomly divided into control group,model group,4-PBA group.The control and model groups were given the same amount of saline,4-PBA group was given 250 mg/kg or 500 mg/kg 4-PBA respectively for 4 weeks,the statuses of hemodynamic(RVSP、mPAP、PASP),right ventricular remodeling index(RVHI)and the percentage of pulmonary vessel wall thickness to vessel diameter(MVT%)were observed in each group.Western blot was used to detect the expressions of protein in lung tissue.The results showed,compared to control group,the value of RVSP,mPAP,PASP,RVHI,MVT%were elevated,and the protein expressions ofα-SMA,Bcl-2 and Bax were significantly increased in the model,which were reversed by 4-PBA.In conclusion,4-PBA can improve hemodynamics,right ventricular and pulmonary vascular remodeling in rats with pulmonary hypertension,which may be related to the down-regulation ofα-SMA,Bcl-2 and Bax protein expression.