Paraquat-induced Pulmonary Fibrosis.

本研究的目的是研究百草枯（PQ）诱导肺纤维化的机制，目的是开发一种治疗肺纤维化的药物。在恒河猴支气管肺泡灌洗液沉积细胞中，PQ主要依赖于中性粒细胞和III型和IV型肺泡巨噬细胞（PAM）的增加。这些类型的PAM增加提示，通过它们的激活，多种生物活性物质，如超氧化物酶和溶酶体酶，可能与pq诱导的肺损伤的发病机制有一定关系。在研究中使用的是大鼠，肺中辅酶的浓度。注射40mg/kg PQ后1 ~ 3 d， Q_9和辅酶Q_<10>均较对照组降低。这一结果支持了PQ毒性的机制是由于动物线粒体中电子传递链的一个重要组成部分受到损伤的概念。在PQ中毒治疗药物的开发研究中，我们研究了n -乙酰- l-半胱氨酸、l-半胱氨酸、l-生育酚- l-抗坏血酸钾、辅酶Q_<10>、氯丙嗪、l-脱氢脯氨酸和牛磺酸等多种能解毒PQ的治疗药物。没有观察到这些几乎是治疗药物对PQ的生物参数和/或致死毒性的影响。然而，牛磺酸（TA）对大鼠急性PQ中毒的影响进行了研究。这一结果表明，长期持续输注5% TA可增加尿量，抑制肾组织中PQ的积累，尽管血液中PQ浓度升高。

The purpose of this investigation is to study the mechanisms of Paraquat (PQ) -induced pulmonary fibrosis with the objective of developing a therapeutic agent for the lung fibrosis.In the sedimentary cells of bronchoalveolar lavage-fluid from rhesus monkeys given PQ were mainly dependent upon the increase of neutrophils and type III and type IV pulmonary alveolar macrophages (PAM). These types of increases in PAM are suggestive that, by their activation, many kinds of biologically active substances, e. g. superoxide and lysosomal enzymes, which might have some relationship to the pathogenesis of PQ-induced pulmonary injury, are released.In the study is using the rats, the concentrations of lung coenzyme. Q_9 and coenzyme Q_<10> were decreased from 1 to 3 days after the 40mg/kg PQ injection compared to the control group. This result supports the concept that the mechanism of PQ toxicity is due to injury of an essential component of the electron transport chain in mitochondria of animals.In the study of development of therapeutic agents for the PQ poisoning, we were investigated many kinds of therapeutic agents, e. g. N-acetyl-L-Cysteine, L-Cystein, dl-tocopherol-L-ascolbic acid potassium, Coenzyme Q_<10>, Chlorpromazine, L-dehydroproline and taurine, which were an able to detoxication of PQ.No effects of these almost therapeutic agents on the bioparameters and/or lethal toxicity of PQ was observed. However, the effect of taurine (TA) on acute PQ intoxication was investigated in rats. This results suggest that a long continuous infusion of 5% TA increased urine output and inhibits of PQ accumulation in renal tissue despite arise in blood PQ concentration.