Studies on the alterations of lung endothelial cells and the metabolism of autacoids during lung diseases

肺部疾病过程中肺内皮细胞变化及自体物质代谢的研究

基本信息

批准号：
60480095
负责人：
ITO Katsuaki
金额：
$ 2.05万
依托单位：
Miyazaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

项目摘要

To learn how lung vascular injury alters the function to metabolize vaso-active autacoids, lung vascular lesions were produced in rats by a single injection of monocrotaline.Three to five weeks after the injection the degeneration or necrotization of lung endothelial cells was observed. When the metabolism of autacoids in lung was evaluated from the difference of responses to i.v. and i.a. injections of substances, the degradation of prostaglandin (PG) <E_2> was suppressed during the monocrotaline-induced lung injury, while the conversion of angiotensin- (A ) to angiotensin- <II> (A <II> ) and the degradation of bradykinin were unaffected.In the next experiments, the effects of autacoids on the mechanical property of pulmonary artery rings isolated from control and monocrotaline-treated rats were examined. Acetylcholine-induced relaxation of rings precontracted by noradrenaline was suppressed in monocrotaline-injured artery suggesting that the production of endothelium-derived relaxing factor (EDRF) is decreased during lung vascular injury. The contraction induced by <PGF_(2> alpha <)> was enhanced in either monocrotaline-injured artery or de-endothelialized artery by rubbing. This enhancement was considered to be due to decreased degradation of PG by endothelial cells. On the other hand, the conversion of A was not altered by endothelial injury because A was probably converted to A <II> by the enzyme present in other sites than endothelium. Canine and bovine pulmonary artery endothelium showed the characteristics similar to that of rats.It is suggested that lung vascular injury impaires the production of EDRF, which may cause pulmonary hypertension, and that the injury may alter the pulmonary and systemic hemodynamics and fluid-electrolyte balance as a result of decreased metabolism of PGs in pulmonary endothelium.

为了了解肺血管损伤如何改变血管活性自体物质的代谢功能，通过单次注射野百合碱在大鼠中产生肺血管损伤。注射后三至五周观察到肺内皮细胞变性或坏死。当根据对静脉注射的反应差异来评估自体激素在肺中的代谢时，和 i.a.注射物质后，野百合碱诱导的肺损伤过程中，前列腺素（PG）<E_2>的降解受到抑制，而血管紧张素-（A）向血管紧张素-<II>（A<II>）的转化）并且缓激肽的降解不受影响。在接下来的实验中，检查了自体激素对从对照和野百合碱治疗的大鼠中分离出的肺动脉环的机械特性的影响。在野百合碱损伤的动脉中，乙酰胆碱诱导的去甲肾上腺素预收缩环的松弛受到抑制，这表明在肺血管损伤期间内皮源性松弛因子（EDRF）的产生减少。 <PGF_(2>α<)>诱导的收缩在野百合碱损伤的动脉或去内皮化的动脉中通过摩擦而增强。这种增强被认为是由于内皮细胞对 PG 的降解减少所致。另一方面，A 的转化并未因内皮损伤而改变，因为 A 可能被存在于内皮以外其他位点的酶转化为 A <II>。犬和牛的肺动脉内皮表现出与大鼠相似的特征，提示肺血管损伤会损害EDRF的产生，从而导致肺动脉高压，并且损伤可能会改变肺和全身的血流动力学和液体电解质平衡由于肺内皮细胞中 PG 的代谢减少。