Effect Of Dichloroacetate On Pulmonary Hypertension In Rat

PartⅠEstablishment of Pulmonary Hypertension Model by Carotid Artery to Jugular Vein Shunt, and Effect of Dichloroacetate on the Model【Objective】To discuss the effect of Dichloroacetate (DCA) on proliferation and apoptosis of pulmonary arterial smooth muscle cells (PASMCs) in pulmonary arterial hypertension (PAH),which is induced by carotid artery to jugular vein shunt.【Methods】It was divided into four groups randomly: Control group, model group, deligation group, and DCA+deligation group, each of which had ten rats. In latter three groups, we separated the left common carotid artery and left external jugular vein, and then induced pulmonary hypertension by end-to-end anastomosis of two vessels. 8 weeks later, the equivalent volume of isotonic Na chloride was given to the control and model groups for 2 weeks. In deligation group, we had ligated the vessel of artery to vein shunt after 8 weeks, the equivalent volume of isotonic Na chloride was given them for 2 weeks. In DCA+deligation group, we had ligated the vessel of artery to vein shunt after 8 weeks, then give DCA(0.75g/L,pH7.0) to them for 2 weeks, the dose was 80mg/kg/d. On week 10, the mean pulmonary arterial pressure (mPAP) of each group had been measured; the media tunica thickness percentage and the right ventricular hypertrophy index were measured; the lung tissue was detected with Hematoxylin-Eosin stain and immunohistochemistry stain. The latter stain was used to show the proliferation (PCNA) and apoptosis (Caspase-3) of PASMCs.【Results】Compared to model group, the mPAP of deligation group and DCA+deligation group had decreased significantly(P < 0.05), but there was no differences between deligation group and DCA+deligation group (P>0.05). Meanwhile, Compared to model group, the media tunica thickness percentage and the right ventricular hypertrophy index (RVHI) of deligation group and DCA+deligation group reduced significantly (P<0.05), but there was no differences between deligation group and DCA+deligation group (P>0.05). PCNA of DCA+deligation group was lower than model group and deligation group (P<0.05), while there was no differences between deligation group and model group(P>0.05). Caspases-3 of DCA+deligation group was higher than model group and deligation group (P<0.05), while there was no differences between deligation group and model group(P>0.05).【Conclusion】DCA has no significant effect on the pulmonary hypertension induced by high lung blood volume, while can restrain proliferation and promote apoptosis.PartⅡEffect of Dichloroacetate on Monocrotaline-Induced Pulmonary Hypertension in Rat【Objective】To discuss the effect of Dichloroacetate (DCA) on proliferation and apoptosis of pulmonary arterial smooth muscle cells (PASMCs) in Monocrotaline-induced pulmonary arterial hypertension (PAH). 【Methods】It was divided into three groups randomly: Control group, model group and DCA group, each of which had ten rats. In the model group and DCA group, the rats were subjected to single subcutaneous injection of MCT (the dose is 60mg/kg) to induce the pulmonary arterial hypertension (PAH). DCA (0.75g/L,pH7.0) was given to DCA group form day 7, the dose of which is 80mg/kg/d. Form the same time on, the equivalent volume of isotonic Na chloride was given to the other two groups. The mean pulmonary arterial pressure (mPAP) of each group had been measured on day 7, 14, 21 and 28; on day 28, the media tunica thickness percentage and the right ventricular hypertrophy index (RVHI) were measured; on day 28, the lung tissue was detected with Hematoxylin-Eosin stain and immunohistochemistry stain. The latter stain was used to show the proliferation (proliferating cell nuclear antigen, PCNA) and apoptosis (Caspase-3) of PASMCs.【Results】The mPAP of DCA group is higher than control group and lower than model group (P<0.05). Meanwhile, The mPAP of model group is higher than control group(P<0.05). Compared with the model group, the mPAP of DCA group had decreased from day 14, which was almost half of the model group on day 28 (P<0.05). Meanwhile, Compared with the model group, the media tunica thickness percentage and the right ventricular hypertrophy index(RVHI) of DCA group reduced significantly (P<0.05). PCNA of DCA group was lower than model group (P<0.05), while Caspase-3 of DCA group was much higher than model group (P<0.05).【Conclusion】Dichloroacetate can reverse pulmonary vascular remodeling through anti-proliferation and pro-apoptosis.