Pääkkö P, Ala-Kokko L, Ryhänen L
Department of Pathology, University of Oulu, Finland.
Eur J Clin Invest. 1987 Aug;17(4):340-6. doi: 10.1111/j.1365-2362.1987.tb02198.x.
Orally administered malotilate was studied as a protective anti-fibrotic agent with respect to experimentally induced pulmonary fibrosis in rats. Intraperitoneally-injected carbon tetrachloride (CCI4) significantly increased the lung weight to body weight ratio, lung total protein and total hydroxyproline content, while the relative protein content of the lungs decreased. CCI4) induction caused diffuse alveolar damage and inflammatory changes mimicking usual interstitial pneumonia with interstitial fibrosis. The morphological findings suggest a primary toxic effect on the lungs. Treatment with malotilate completely normalized the lung weight to body weight ratio, lung total and relative protein content and total hydroxyproline content. Morphologically, malotilate seemed to prevent the exudative inflammatory changes and interstitial fibrosis, but not the primary toxic effect of CCI4 on the capillary endothelium or the alveolar epithelium, the result of which was diffuse alveolar damage. It is concluded that malotilate may be a useful drug for the prevention of pulmonary fibrosis.
研究了口服马洛替酯作为一种保护性抗纤维化药物对大鼠实验性诱导肺纤维化的作用。腹腔注射四氯化碳(CCI4)显著增加了肺重量与体重的比值、肺总蛋白和总羟脯氨酸含量,而肺的相对蛋白含量降低。CCI4诱导引起弥漫性肺泡损伤和炎症变化,类似于伴有间质纤维化的寻常型间质性肺炎。形态学结果提示对肺有原发性毒性作用。用马洛替酯治疗可使肺重量与体重的比值、肺总蛋白和相对蛋白含量以及总羟脯氨酸含量完全恢复正常。形态学上,马洛替酯似乎可预防渗出性炎症变化和间质纤维化,但不能预防CCI4对毛细血管内皮或肺泡上皮的原发性毒性作用,其结果是弥漫性肺泡损伤。结论是马洛替酯可能是预防肺纤维化的一种有用药物。