Roth R A, Ganey P E
Am Rev Respir Dis. 1987 Sep;136(3):762-5. doi: 10.1164/ajrccm/136.3.762.
MCT produces pulmonary vascular injury and pulmonary hypertension in rats by unknown mechanisms and provides a useful animal model with which to study chronic pulmonary hypertension. Several arachidonic acid metabolites including TxA2 and LT are present in increased concentration in lungs of rats made chronically pulmonary hypertensive with MCT or MCTP. The lack of protection afforded by cotreatment with drugs that inhibit the biosynthesis or antagonize the actions of TxA2 indicates that TxA2 does not play a major role in the pathogenesis of cardiopulmonary injury in this model. Results with DEC suggest the possibility of involvement of LT in the response to MCT and MCTP; additional work is needed to clarify the exact role of LT in this model. The roles of other biologically active lipid mediators such as platelet activating factor and HETEs are currently unknown. Increased understanding of the role of various mediators will come partly from the identification and careful use in vivo of improved drugs that have specific effects as synthesis inhibitors or receptor antagonists.
MCT 通过未知机制在大鼠中引发肺血管损伤和肺动脉高压，为研究慢性肺动脉高压提供了一种有用的动物模型。在经 MCT 或 MCTP 诱导产生慢性肺动脉高压的大鼠肺中，包括血栓素 A2（TxA2）和白三烯（LT）在内的几种花生四烯酸代谢产物浓度升高。与抑制生物合成或拮抗 TxA2 作用的药物联合治疗未提供保护作用，这表明 TxA2 在该模型的心肺损伤发病机制中不发挥主要作用。DEC 的结果提示 LT 可能参与了对 MCT 和 MCTP 的反应；需要进一步开展工作以阐明 LT 在该模型中的具体作用。其他生物活性脂质介质如血小板活化因子和羟基二十碳四烯酸（HETEs）的作用目前尚不清楚。对各种介质作用的深入了解部分将来自于体内对具有合成抑制或受体拮抗等特定作用的改良药物的鉴定和谨慎使用。
