四氢吡咯二硫代氨基甲酸酯对百草枯致大鼠肺损伤的干预研究

目的]探讨四氢吡咯二硫代氨基甲酸酯(pyrrolidine dithiocarbamate,PDTC)对抗百草枯(paraquat,PQ)致肺损伤的作用。方法]54只健康雄性SD大鼠随机分为对照组(生理盐水)、单纯染毒组(4组)和干预组(4组)。PQ经口给药,剂量40 mg/kg,干预组给予PQ后立即腹腔注射,PDTC 120 mg／kg。在染毒后第3、7、14、2l天各取一组动物进行检查,检测血浆和支气管-肺泡灌洗液(BALF)中丙二醛(MDA)含量、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力、肺组织匀浆中羟辅氨酸(HYP)含量,并观察肺组织病理改变。结果]PQ 40mg/kg染毒后血浆和BALF中MDA含量增加,GSH-Px、SOD活力减弱,与对照组相比,相应时点差异有统计学意义(P<0．01);给予PDTC 120 mg／kg干预以后,使GSH-Px与SOD活力升高,MDA含量减少,相应时点差异有统计学意义(P<0．05或P<0．01)。血浆中与BALF中的GSH-Px,SOD活力及MDA含量存在正相关(P<0．05)。同时,单纯染毒组第7、14、21天的HYP含量比对照组显著升高,差异有统计学意义(P<0．01),但干预组HYP含量较单纯染毒组低。病理观察可见干预组肺组织水肿、出血及炎性细胞浸润程度减轻。结论]PDTC干预后可以升高SOD、GSH-Px活力,减少MDA的产生和胶原聚集,提示PDTC可能改善PQ中毒所引起的肺损害。

Effect of Pyrrolidine Dithiocarbamate( PDTC )on the Pulmonary Damage Induced by Paraquat in Rats

Objective] To investigate the potential protective effect of pyrrolidine dithiocarbamate (PDTC)on the pulmonary damage induced by paraquat in rats. Methods]Fifty-four healthy male SD rats were randomly assigned into the paraquat (PQ) -treated (4 groups), the PDTC treatment (4 groups), and the control group (normal saline). Rats were administrated with 40 mg/kg of PQ intragastrically in the first 4 groups, and with 40 mg/kg of PQ plus 120 mg/kg PDTC via i.p. simultaneously in PDTC treatment groups. On the 3rd, the 7th, the 14th, and 28th day after treatments, one group of rats of each treatments were sacrificed, and the level of maleic dialdehyde(MDA), and the activity of superoxide dismutase(SOD)and glutathione peroxidase (GSH-Px) both in plasma and bronchoalveolar lavage fluid (BALF) of rats in each group, as well as the content of hydroxyproline (HYP) in lung homogenate were detected. Meanwhile, pathological changes of lungs were examined under optical microscope. Results] The level of MDA in plasma and blood increased and the activity of GSH-Px and SOD decreased with positive significance compared with the control group(P<0.01)after the treatment of PQ 40 mg/kg in corresponding sacrifice dates. In comparison with PQ treated group, with the treatment of PDTC(120 mg/kg), the activities of SOD and GSH-Px in PDTC-treated group increased significantly, while the level of MDA decreased with the positive difference(P<0.05 or P<0.01) in the corresponding sacrifice dates. Meanwhile, the level of HYP in PQ treated group was significantly higher than the control (P<0.01), and its content in the PDTC-treated group was lower than that of PQ group. The histological changes such as alveolar edema, hemorrhage and inflammatory cell infiltration in the PDTC-treated group were slighter than those in PQ group. Conclusion] Treatment of PDTC could increase the activities of SOD and GSH-Px, and bring down the production of MDA and the production of HYP. It suggested that PDTC could alleviate the lipid peroxidation damage in paraquat treated rats to some extent.