机构地区:[1]第四军医大学基础部病理生理学教研室,陕西西安710032
出 处:《中国应用生理学杂志》2007年第4期473-477,共5页Chinese Journal of Applied Physiology
摘 要:目的:观察间断性减压低氧大鼠出、入肺血血浆、肺组织匀浆和体循环动脉匀浆中内皮素-1(ET-1)的含量变化,以及出、入肺血血清中血管内皮生长因子(VEGF)的含量变化及其与低氧性肺动脉高压的关系。方法:建立间断性减压低氧模型,采用插管法分别测定左侧颈总动脉压力(CAP)、右心室平均压分别代表体循环压力和平均肺动脉压力(mPAP),放射免疫测定法测定ET-1含量,双抗体夹心ABC-ELISA法测定VEGF含量。结果:①低氧2周组(H2)、低氧3周组(H3)大鼠平均肺动脉压力、右心肥厚指数(RV/LV+S)均分别显著高于对照组,而各组平均颈动脉压力之间无明显变化(P>0.05)。②对照组大鼠出肺血中ET含量比入肺血中低(P<0.05),H2、H3组大鼠出、入肺血中ET-1含量较对照组均明显增高(P<0.01),且H2、H3组大鼠出肺血中ET-1含量均高于入肺血中ET-1含量(P<0.05),刚好与对照组相反。H2、H3组大鼠肺组织匀浆中ET-1含量与对照组肺组织和低氧组体循环动脉组织匀浆比较,均明显增高(P<0.01),而各组体循环动脉组织匀浆中ET-1含量间无明显差异(P>0.05)。③对照组大鼠出、入肺血中VEGF含量无明显差异(P>0.05),H2、H3组大鼠出肺血血清中VEGF含量较对照组明显增高(P<0.01)。结论:在慢性低氧可使肺组织产生ET-1和VEGF增多,这可能是慢性肺动脉高压发生、发展的重要机制之一。肺动脉局部缩血管物质ET-1增高,而体循环动脉局部ET-1不增高,可能是长期慢性低氧可导致肺动脉高压的形成,却不发生高血压的机制之一。To study the effects of endothelin-1 (ET-1 ) and vascular endothelial growth factor(VEGF) on the mechanism of hypoxic pulmonary hypertension(HPH). Methods: We studied 4 groups of age-controlled male rats, i.e. normal control for 2 weeks group (N2), normal control for 3 weeks group (N3), exposed to hypoxia for 2 weeks group (H2) and for 3 weeks group (H3). Chronic HPH rat models were established by chronic hypobaric hypoxia[ ( 10.0 % ± 0.5 %O2 ] for 2 and 3 weeks, respectively. The rats were anesthetized and fixed, and the levels of mean pulmonary artery pressure(mPAP) and carotid arterial pressure(CAP) were measured using catheters by a microcomputer via transducers. The weight ratio of right ventricle(RV) and left ventricle and septum(LV + S)[RV/( LV + S] were determined. The contents of ET-1 in plasma of pulmonary artery and carotid artery and in homogenates of lung and systemic arteries were determined by radioimmunoassay, and the contents of VEGF in serum of pulmonary artery and carotid artery were determined by ABC-ELISA. Results: HPH rat models were established successfully. Compared with control groups, the values of ET-1 were both enhanced in carotid artery and pulmonary artery plasma in model groups( P〈0.01 ). In the HPH groups, the level of pulmonary artery plasma ET-1 was significantly lower than that of carotid artery plasma, but just the reverse was ET-1 in control rats. The levels of ET-1 in homogenates of lungs from HPH models were significantly higher than those in homogenates of lungs from control groups( P 〈 0.01 ), and markedly higher than those in homogenates of systemic arteries from HPH rats( P 〈 0.01 ) . The values of VEGF in serum of pulmonary artery from H3 group were significantly higher than those from control groups and H2 group(P〈0.01). In serum of carotid artery, the values of VEGF from the HPH models were higher than those from the control groups( P 〈 0.01 ). Conclusion: ET- 1 and VEGF play impo
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