Bruner L H, Johnson K J, Till G O, Roth R A
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Am J Physiol. 1988 Feb;254(2 Pt 2):H258-64. doi: 10.1152/ajpheart.1988.254.2.H258.
Monocrotaline pyrrole (MCTP) causes pulmonary vascular injury, pulmonary hypertension, and right ventricular hypertrophy in rats. The mechanisms by which MCTP causes lung injury are not known. After treatment with a moderate dose of MCTP, several days pass before major lung injury is detected, thus suggesting that the damage is caused indirectly. Since activation of the complement system can cause lung injury, it was of interest to test whether complement activation may be important in lung injury due to MCTP. Accordingly, rats were given a single dose of MCTP (3.5 mg/kg iv), and serum hemolytic complement activity was measured at several times after rats were treated. Neutrophil aggregometry also was used to determine whether complement activation products could be detected in serum after MCTP was given in vivo. The effect of complement depletion on MCTP-induced pulmonary injury was tested by cotreating rats with purified cobra venom factor and MCTP. MCTP treatment did not cause detectable complement activation in vivo, and complement depletion did not protect rats from lung injury. The direct effect of MCTP on serum complement also was tested by exposing fresh rat serum to MCTP in vitro and measuring serum complement activity. MCTP decreased serum hemolytic complement activity in vitro, but it did not interfere with subsequent zymosan-induced activation of complement. These results suggest that complement does not play a role in the development of major lung injury that occurs several days after treatment of rats with MCTP.
野百合碱吡咯（MCTP）可导致大鼠肺血管损伤、肺动脉高压和右心室肥大。MCTP导致肺损伤的机制尚不清楚。用中等剂量的MCTP治疗后，数天之后才能检测到严重的肺损伤，因此提示损伤是间接造成的。由于补体系统的激活可导致肺损伤，所以研究补体激活在MCTP所致肺损伤中是否起重要作用很有意义。因此，给大鼠静脉注射单剂量的MCTP（3.5mg/kg），并在给药后的不同时间测量血清溶血补体活性。还采用中性粒细胞凝集测定法来确定在体内给予MCTP后血清中是否能检测到补体激活产物。通过用纯化的眼镜蛇毒因子与MCTP联合处理大鼠，来测试补体耗竭对MCTP诱导的肺损伤的影响。MCTP治疗在体内未引起可检测到的补体激活，补体耗竭也不能保护大鼠免受肺损伤。通过在体外将新鲜大鼠血清暴露于MCTP并测量血清补体活性，来测试MCTP对血清补体的直接作用。MCTP在体外降低了血清溶血补体活性，但不干扰随后酵母聚糖诱导的补体激活。这些结果提示补体在大鼠用MCTP治疗数天后发生的严重肺损伤的发展过程中不起作用。
