肝素抑制低氧性肺动脉高压大鼠肺血管内皮生长因子1的表达

Inhibitory effect of heparin on hypoxia-induced pulmonary hypertension and changes of vascular endothelial growth factor 1 in rats

目的:观察肝素抑制大鼠低氧性肺动脉高压过程中,血管内皮生长因子1(VEGF-1)在肺小动脉血管内皮细胞和肺组织中的表达变化。方法:成年雄性SD大鼠24只,随机分为对照组(A组)、低氧4周组(B组)和低氧+肝素4周组(C组),每组8只。测各组大鼠平均肺动脉压(mPAP)、右室肥大指数(RVHI)和血管形态学指标;HE染色观察肺动脉血管形态学改变,免疫组化法检测肺动脉血管内皮细胞VEGF-1蛋白表达;RT-PCR检测肺组织VEGF-1基因表达。结果:mPAP、RVHI、肺小动脉重塑指标、肺小动脉血管内皮细胞VEGF-1蛋白表达和肺组织VEGF-1基因表达水平在C组高于A组,低于B组。相关分析表明,VEGF-1蛋白表达与肺血管重塑呈正相关(r=0.974,P<0.01)。VEGF-1 mRNA与VEGF-1蛋白呈正相关(VEGF120 mRNA,r=0.919,P<0.01;VEGF164 mRNA,r=0.896,P<0.01)。结论:肝素可能在转录和翻译水平抑制VEGF-1的表达,从而抑制大鼠低氧性肺动脉高压的形成。

AIM： To observe the protein expression of vascular endothelial growth factor 1 （ VEGF - 1 ） in pulmonary arterial endothelial cells and VEGF - 1 gene expression in lung tissue in rats with hypoxia - induced pulmonary hypertension and treated with heparin. METHODS ： Twenty four male adult SD rats were randomly divided into three groups （8 rats each） ： a control group （group A）, a group with hypoxia for 4 weeks （group B） and a group with hypoxia for 4 weeks and injected with heparin to abdominal cavity simultaneously （group C ）. Mean pulmonary arterial pressure （mPAP）, right ventricle hypertrophy index （RVHI） and vessel morphometry were measured. The morphology of pulmonary artery was observed by HE staining. The expression of VEGF - 1 protein in pulmonary arterial endothelial cells was determined by immunohistochemistry. The level of VEGF - 1 mRNA in lung tissue was measured by reverse transcription polymerase chain reaction （RT - PCR）. RESULTS： mPAP, RVHI, pulmonary artery remodeling parameters, VEGF - 1 protein expression in pulmonary arterial endothelial cells and VEGF - 1 gene expression in lung tissue of the three groups from high to low were group B, group C and group A. It was statistically significant when compared between either two groups of the three （ P 〈 0. 01 ）. Linear correlation analysis showed that VEGF - 1 protein was positively correlated with pulmonary artery remodeling parameters （ r = 0. 974, P 〈 0. 01 ） , and VEGF - 1 mRNA was positively correlated with VEGF - 1 protein （VEGF 120 mRNA, r = 0. 919, P 〈 0. 01 ; VEGF164 mRNA, r = 0. 896, P 〈 0. 01 ）. CONCLUSION： Heparin may down - regulate the expression of VEGF - 1 at the levels of transcription and translation, resulting in the inhibitory effect on rats with hypoxia- induced pulmonary hypertension.