Woods L W, Wilson D W, Schiedt M J, Giri S N
Department of Veterinary Pathology, School of Veterinary Medicine, University of California, Davis 95616.
Am J Pathol. 1993 Jan;142(1):129-38.
Effects of a single dose of 3-methylindole (3-MI) (250 mg/kg intraperitoneally) were studied at different times ranging from 12 hours to 2 weeks post-treatment (PT). Microscopic study revealed mild Clara cell injury 24 hours PT and mucus hyperplasia 24 hours to 2 weeks PT. Diffuse type I alveolar epithelial cell necrosis occurred at 48 hours, followed by type II cell hyperplasia. Septal edema and accumulation of interstitial and capillary polymorphonuclear leukocytes and perivascular mixed mononuclear inflammatory cells accompanied the injury and repair. A gradual resolution of lesions with persistent mononuclear inflammatory cellular clusters at septal junctions, focal septal fibrosis, and accumulation of alveolar macrophages was evident at 1 and 2 weeks PT. Collagen, measured as hydroxyproline, in 3-MI-treated rats was significantly increased to 130% and 139% of control (3.0 mg/lung) at 1 and 2 weeks PT, respectively. Biphasic peaks of plasma 6-keto-prostaglandin F1 alpha occurred at 12 to 24 hours and at 96 hours PT with 3-MI and thromboxane B2 was elevated 12, 48, and 96 hours PT. Right ventricular/left ventricular and septal weight was increased to 120% and 140% of the control 1 and 2 weeks PT. We concluded that 3-MI induces alveolar septal injury in the rat with relatively complete repair of the alveolar epithelium and residual mild focal septal fibrosis and pulmonary hypertension 2 weeks PT. Arachidonic acid-derived mediators and inflammation are associated with 3-MI-induced lung injury.
研究了单次腹腔注射3 - 甲基吲哚（3 - MI，250 mg/kg）在治疗后12小时至2周不同时间的影响。显微镜检查显示，治疗后24小时出现轻度克拉拉细胞损伤，治疗后24小时至2周出现黏液增生。48小时出现弥漫性I型肺泡上皮细胞坏死，随后II型细胞增生。损伤和修复过程伴有间隔水肿、间质和毛细血管多形核白细胞以及血管周围混合单核炎性细胞的积聚。治疗后1周和2周，病变逐渐消退，间隔连接处持续存在单核炎性细胞簇、局灶性间隔纤维化以及肺泡巨噬细胞积聚明显。以羟脯氨酸衡量的3 - MI处理大鼠的胶原蛋白在治疗后1周和2周分别显著增加至对照组（3.0 mg/肺）的130%和139%。3 - MI处理后，血浆6 - 酮 - 前列腺素F1α在12至24小时和96小时出现双相峰值，血栓素B2在治疗后12、48和96小时升高。治疗后1周和2周，右心室/左心室和室间隔重量分别增加至对照组的120%和140%。我们得出结论，3 - MI可诱导大鼠肺泡间隔损伤，肺泡上皮相对完全修复，治疗后2周残留轻度局灶性间隔纤维化和肺动脉高压。花生四烯酸衍生介质和炎症与3 - MI诱导的肺损伤有关。
