Ofulue A F, Sekhon H, Cherukupalli K, Khadempour H, Thurlbeck W M
Department of Pathology, University of British Columbia, Vancouver, Canada.
Pediatr Pulmonol. 1991;10(1):46-51. doi: 10.1002/ppul.1950100110.
To determine the role of calmodulin in postnatal lung growth and development, 4-week-old rats were injected intraperitoneally on consecutive days with trifluoperazine (TFP), a potent and specific calmodulin antagonist, for a period fo 3 weeks and studied in comparison with normal controls and undernourished weight-matched animals. TFP treatment resulted in stunting of lung growth such that observed normal increments in morphometrically determined total number of alveoli and alveolar surface area and in biochemically determined DNA, elastin, and collagen contents of the lungs were diminished in comparison with age-matched normal controls. However, the TFP treatment also resulted in reduced daily food intake and body weight gain. In the TFP group, lung weight and lung volume were also reduced compared with the weight-matched control group. This resulted in reduced alveolar surface area, total number of alveoli, DNA, collagen, and elastin in the TFP group compared with values in the weight-matched controls. Thus the TFP-induced lung changes were not due to inanition and/or reduced somatic growth. The TFP treatment resulted in reduced activities of calmodulin and cyclic adenosine monophosphate (cAMP)-phosphodiesterase in the lungs of the animals, independent of their nutritional status. Based on these findings, we suggest that calmodulin may be an important regulatory component of postnatal lung growth and development.
为了确定钙调蛋白在出生后肺生长发育中的作用，对4周龄大鼠连续3周腹腔注射三氟拉嗪（TFP，一种强效且特异性的钙调蛋白拮抗剂），并与正常对照组和营养不足但体重匹配的动物进行比较研究。TFP治疗导致肺生长发育迟缓，与年龄匹配的正常对照组相比，形态学测定的肺泡总数和肺泡表面积以及生化测定的肺组织DNA、弹性蛋白和胶原蛋白含量的正常增加均减少。然而，TFP治疗也导致每日食物摄入量和体重增加减少。在TFP组中，与体重匹配的对照组相比，肺重量和肺体积也降低。这导致TFP组的肺泡表面积、肺泡总数、DNA、胶原蛋白和弹性蛋白与体重匹配的对照组相比降低。因此，TFP诱导的肺变化并非由于营养不良和/或体细胞生长减少所致。TFP治疗导致动物肺中钙调蛋白和环磷酸腺苷（cAMP）磷酸二酯酶的活性降低，与它们的营养状况无关。基于这些发现，我们认为钙调蛋白可能是出生后肺生长发育的重要调节成分。
