肝素通过增加细胞周期抑制因子p27减轻大鼠低氧性肺动脉高压

Heparin Alleviates Hypoxic Pulmonary Hypertension Through Upregulating p27

目的:研究肝素防治大鼠低氧性肺动脉高压的作用机制。方法:复制慢性低氧性肺动脉高压大鼠模型,将大鼠分为常氧对照组(Hypoxia),常氧加肝素组(Normoxia+H),缺氧模型组(Hypoxia)及缺氧加肝素组(Hypoxia+H)共四组。待模型复制完毕后,测定大鼠RVPSP和RV/LV+S,然后进行组织病理分析,测定MA%和MT%以确定肺动脉高压的程度。利用Western-blot实验与RT-PCR实验检测肺动脉中p27蛋白水平及RNA水平的变化。结果:慢性低氧显著增加了大鼠RVPSP、RV/LV+S、MA%和MT%,引起了大鼠肺动脉压力的增高、右心室肥厚和肺中小动脉的中膜增厚及外膜增生,肝素的使用减轻了慢性缺氧条件下大鼠的RVPSP和RV/LV+S,降低了MA%和MT%,有效降低了肺动脉高压、右心室肥厚,并减轻了肺中小动脉的中膜增厚和外膜增生。Western-blot实验发现使用肝素的缺氧组大鼠肺动脉中p27蛋白表达增加,而RT-PCR实验发现p27的转录水平变化不显著。结论:结果显示肝素可能通过增加p27的表达,从而抑制肺动脉平滑肌细胞的增殖,减轻了肺动脉血管的狭窄及降低了肺动脉高压。

Objective： To explore the alleviating effects of heparin on chronic hypoxia induced pulmonary hypertension and investigate the underlying mechanism.Methods： Male SD rats were assigned into four groups treated with or without heparin.The different groups of rats were challenged by intermittent chronic hypoxia exposure for four weeks.Then we get the hypoxic pulmonary hypertension rat models.Subsequently,hemodynamic and pulmonary pathomorphology data were gathered.Western blotting or reverse transcriptional polymerase chain reaction（RT-PCR） were adopted to test p27 changes in rat pulmonary artery.Results： Heparin effectively attenuated hypoxic pulmonary hypertension and elevated the expression of p27.Conclusion： Heparin can effectively relieve hypoxic pulmonary hypertension.The mechanism underlying the effects of heparin might be upregulation of p27.