氧化应激及核因子-kB在百草枯致大鼠肺损伤中的变化  

Change of oxidative stress and nuclear factor-K B in acute paraquat poisoned rats

作　　者：黄敏[1] 张平[1] 常秀丽[1] 吴庆[1] 周志俊[1] 

机构地区：[1]复旦大学公共卫生学院,教育部公共卫生安全重点实验室,上海200032

出　　处：《中华劳动卫生职业病杂志》2009年第8期457-462,共6页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家科技支撑计划（2006BA106801）;上海市公共卫生重点学科建设项目（08GWZX0303）;上海市学科带头人培养计划（08GWD20）

摘　　要：目的观察急性百草枯（PQ）中毒大鼠氧化应激及肺组织核因子-KB（NF—KB）的变化，探讨四氢吡咯二硫代氨基甲酸酯（PDTC）的治疗机制。方法SD大鼠144只随机分为对照组6只、PDTC对照组36只、PQ染毒组56只、PDTC治疗组46只。染毒组和治疗组予生理盐水稀释PQ80mg／kg一次性灌胃后2h，治疗组给予PDTC100mg／kg一次性腹腔注射，染毒组予等量生理盐水腹腔注射；对照组和PDTC对照组于生理盐水1ml／kg灌胃后2h，PDTC对照组予PDTC100mg／kg一次性腹腔注射，对照组予等量生理盐水腹腔注射。不同处理后1、3、7、14、25、56d观察大鼠肺组织病理改变；测定血清中丙二醛（MDA）含量及谷胱甘肽过氧化物酶（GSH—Px）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、髓过氧化物酶（MPO）活力；测定肺组织中羟脯氨酸（Hyp）含量及NF—KBp65的表达。结果与对照组比较，染毒组血清中MDA含量和MPO活力升高，GSH—Px、CAT、SOD活力降低，相应时点差异有统计学意义（P〈0．05或P〈0．01）；肺组织NF—KB活性在1、3、7、14d明显升高，肺组织Hyp含量在14、28、56d明显升高，差异均有统计学意义（P〈0．01）。PDTC治疗组血清中MDA含量降低，GSH—Px、CAT、SOD活力升高，与染毒组比较，相应时点差异均有统计学意义（P〈0．05或P〈0．01），在14dMPO活力为（119．56±21．23）U／L，明显低于染毒组，差异有统计学意义（P〈0．05）；与染毒组比较，治疗组在1、3、7d肺组织中NF-KB活性明显降低，差异有统计学意义（P〈0．05或P〈0．01）；治疗组肺组织中Hyp含量在28、56d分别为（0．89±0．05）、（0．93±0．13）μg/mg，明显低于染毒组，差异有统计学意义（P〈0．01）；病理检查结果显示，治疗组肺组织炎症及纤维化程度均较轻。结论氧化应激及NF-KB活化是参与PQ致肺损伤的重要机制；PDTC能纠正氧化还原�Objective To investigate the change of oxidative stress and nuclear factor-KB （NF-KB） activity in acute paraquat （PQ） poisoned rats and the effect of PDTC. Methods 144 SD rats were randomly di- vided into four experimental groups： control group （6 rats）, PDTC group （36 rats）, PQ group （56 rats） and PQ＋ PDTC group （46 rats）. On the 1st, the 3rd, the 7th, the lgth, the 28th and the 56th day after treatment, the level of malondialdehyde （MDA）, the activity of glutathione peroxidase （GSH-Px）, superoxide dismutase （SOD）, catalase （CAT） and myeloperoxidase （MPO） in serum were detected; the content of hydroxyproline （Hyp） and the activity of NF-KB in lung tissues were detected; the lung pathological changes of rats were observed. Results The level of MDA and MPO in serum increased and the activity of GSH-Px, SOD, CAT in serum decreased sig- nificantly in PQ group compared with control and PDTC group （P〈0.05 or P〈0.O1） in the corresponding sacrifice dates. There were a significant decrease of MDA and increase of GPx, SOD, CAT in PQ ＋PDTC group compared with PQ group （P〈0.05 or P〈0.01） in the corresponding sacrifice dates. The activity of NF-KB in lung tissue of PQ group significantly increased on the 1st, the 3rd, the 7th and 14th day compared with control and PDTC group （P〈0.01）.There was a significant decrease in NF-KB activity on the 1st, the 3 rd, the 7th day in PQ＋PDTC group compared with PQ group （P〈0.05 or P〈0.01）. The MPO activity on the 14th day was（ 119.56± 21.23 ）U/L, was lower than that of PQ group （P〈0.05）. Meanwhile, the content of Hyp in PQ group was significantly higher than control and PDTC group on the 14th, the 28th and the 56th day （P〈0.01）, and its content was lower in PQ＋PDTC group on the 28th and the 56th day （0.89±0.05）,（0.93±0.13） μg/mg compared with PQ group （P〈0.01）. The histological changes such as alveolitis and fibrosis in PQ＋PDTC group were slighter than those in PQ gr

关 键 词：百草枯 肺损伤 氧化应激 NF-KB 四氢吡咯二硫代氨基甲酸酯 

分 类 号：R686[医药卫生—骨科学]