Bruner L H, Bull R W, Roth R A
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Toxicol Appl Pharmacol. 1987 Oct;91(1):1-12. doi: 10.1016/0041-008x(87)90188-8.
Monocrotaline pyrrole (MCTP) is a pyrrolizidine alkaloid that causes pulmonary vascular injury and pulmonary hypertension in rats. The lesions in lungs of MCTP-treated rats are similar to those occurring in humans with primary pulmonary hypertension. Thus, the MCTP-treated rat is a good animal model for this disease. The mechanisms by which MCTP causes lung injury are unknown. The character of the pulmonary lesions and the delay in onset of the injury after a single low dose of MCTP suggest that immune mechanisms may be important in the pathogenesis. Accordingly, rats were treated with MCTP and the immunosuppressants antilymphocyte serum (ALS) or cyclosporin A (CyA). Neither ALS nor CyA completely protected rats from the injury due to MCTP. Several series of experiments also were undertaken to assess the effect of lymphocytes adoptively transferred from MCTP-treated donor rats into MCTP-treated recipient rats. Adoptive transfer of lymphocytes did not decrease the onset time of the injury or increase the severity of lesions due to MCTP in the recipients. These results indicate that immune mechanisms are probably not involved in MCTP-induced pulmonary injury.
单克尿他林吡咯（MCTP）是一种吡咯里西啶生物碱，可导致大鼠肺血管损伤和肺动脉高压。MCTP处理的大鼠肺部病变与原发性肺动脉高压患者的病变相似。因此，MCTP处理的大鼠是这种疾病的良好动物模型。MCTP导致肺损伤的机制尚不清楚。肺部病变的特征以及单次低剂量MCTP后损伤的延迟发作表明免疫机制可能在发病机制中起重要作用。因此，用MCTP和免疫抑制剂抗淋巴细胞血清（ALS）或环孢素A（CyA）处理大鼠。ALS和CyA均不能完全保护大鼠免受MCTP所致的损伤。还进行了一系列实验，以评估从MCTP处理的供体大鼠向MCTP处理的受体大鼠过继转移淋巴细胞的效果。淋巴细胞的过继转移并未减少受体中MCTP所致损伤的发作时间或增加损伤的严重程度。这些结果表明免疫机制可能不参与MCTP诱导的肺损伤。
