Chen M J, Chiang L Y, Lai Y L
Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan 100.
Toxicol Appl Pharmacol. 2001 Mar 15;171(3):165-73. doi: 10.1006/taap.2000.9117.
We attempted to evaluate whether the antioxidants 1,3-dimethyl-2-thiourea (DMTU) and hexa(sulfobutyl)fullerenes (FC(4)S) attenuate monocrotaline (MCT)-induced pulmonary hypertension (PH) by lowering lung substance P (SP) in Wistar rats. Sixty-three rats weighing 297 +/- 8 g were divided into six groups: control; MCT; capsaicin + MCT; MCT + DMTU-1; MCT + DMTU-2; and MCT + FC(4)S. Three weeks before the functional study, saline was injected into each control rat, whereas each MCT rat received 60 mg/kg sc MCT. Rats in the third group received capsaicin pretreatment followed by MCT. A 3-day injection of DMTU was performed during the early (DMTU-1) or the late (DMTU-2) post-MCT period. For the last group, each MCT-treated rat received a daily FC(4)S injection until the commencement of the functional study. Compared to the control group, MCT caused significant increases in pulmonary arterial pressure (Ppa), right ventricular hypertropy, pulmonary arterial medial thickness, lung SP level, and luminol-enhanced chemiluminescence counts in bronchoalveolar lavage. Both capsaicin and antioxidants significantly attenuated the above MCT-induced alterations. SP-induced acute increase in Ppa was exaggerated in MCT-treated rats. These results suggest that oxygen radicals play an important role in MCT-induced PH via elevating lung SP level.
我们试图评估抗氧化剂1,3 - 二甲基 - 2 - 硫脲（DMTU）和六（磺丁基）富勒烯（FC(4)S）是否通过降低Wistar大鼠肺组织中的P物质（SP）来减轻野百合碱（MCT）诱导的肺动脉高压（PH）。将63只体重为297±8 g的大鼠分为六组：对照组；MCT组；辣椒素+ MCT组；MCT + DMTU - 1组；MCT + DMTU - 2组；以及MCT + FC(4)S组。在功能研究前3周，给每只对照大鼠注射生理盐水，而每只MCT组大鼠皮下注射60 mg/kg MCT。第三组大鼠先接受辣椒素预处理，然后注射MCT。在MCT注射后的早期（DMTU - 1）或晚期（DMTU - 2）进行为期3天的DMTU注射。对于最后一组，每只接受MCT处理的大鼠每天注射FC(4)S，直至功能研究开始。与对照组相比，MCT导致肺动脉压（Ppa）、右心室肥厚、肺动脉中层厚度、肺SP水平以及支气管肺泡灌洗中鲁米诺增强的化学发光计数显著增加。辣椒素和抗氧化剂均显著减轻了上述MCT诱导的改变。在MCT处理的大鼠中，SP诱导的Ppa急性升高更为明显。这些结果表明，氧自由基通过升高肺SP水平在MCT诱导的PH中起重要作用。
