Kuttan R, Lafranconi M, Sipes I G, Meezan E, Brendel K
Res Commun Chem Pathol Pharmacol. 1979 Aug;25(2):257-68.
Morphological evidence has shown that the herbicide paraquat produces severe lung fibrosis in experimental animals. In order to investigate the biochemical basis for this fibrosis, prolyl hydroxylase activity, total hydroxyproline content and collagen and protein synthesis were estimated in rats (200 gm) which were pretreated with paraquat (25 mg/Kg; I.P.) nine days before sacrifice. Prolyl hydroxylase activity in the treated rats was significantly elevated in the lungs. However, no such increase was seen in the kidney. There was no significant change in the total hydroxyproline content or collagen formation in the treated animals. When paraquat was added to the culture medium and incubated with lung slices, there was a marked decrease in collagen synthesis along with a decrease in protein synthesis. When paraquat was added to lung cells in culture, it was found that lung explants were more sensitive to paraquat toxicity than cells obtained by trypsinization. In explants which were sensitive to paraquat, there was a marked decrease in both protein synthesis and collagen synthesis.
形态学证据表明,除草剂百草枯在实验动物中会导致严重的肺纤维化。为了探究这种纤维化的生化基础,在处死前九天用百草枯(25mg/Kg;腹腔注射)预处理大鼠(200克),并对其脯氨酰羟化酶活性、总羟脯氨酸含量以及胶原蛋白和蛋白质合成进行了评估。经处理的大鼠肺部脯氨酰羟化酶活性显著升高。然而,在肾脏中未观察到这种增加。经处理的动物总羟脯氨酸含量或胶原蛋白形成没有显著变化。当将百草枯添加到培养基中并与肺切片一起孵育时,胶原蛋白合成显著减少,同时蛋白质合成也减少。当将百草枯添加到培养的肺细胞中时,发现肺外植体比通过胰蛋白酶消化获得的细胞对百草枯毒性更敏感。在对百草枯敏感的外植体中,蛋白质合成和胶原蛋白合成均显著减少。