核因子-kB及细胞因子在百草枯致大鼠肺损伤中的动态变化  

Changes of cytokine and nuclear factor-kappa B in acute paraquat poisoned rats

作　　者：黄敏[1] 张平[1] 常秀丽[1] 顾锡安[1] 吴庆[1] 周志俊[1] 

机构地区：[1]复旦大学公共卫生学院劳动卫生教研室,上海200032

出　　处：《中华劳动卫生职业病杂志》2009年第8期463-467,共5页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：基金项目：国家科技支撑计划（编号：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）中毒大鼠细胞因子白介素-1β（IL-1β）、转化生长因子一B1（TGF-β1）、肿瘤坏死因子-α（TNF-α）、血小板源性生长因子（PDGF）和肺组织核因子-kappaB（NF-KB）的变化及四氢吡咯二硫代氨基甲酸酯（PDTC）的干预效果，以探讨百草枯致肺损伤机制。方法SD大鼠随机分为对照组6只、PQ染毒组56只、PDTC干预组46只。染毒组和干预组给予生理盐水稀释PQ80mg／kg一次性灌胃后2h，染毒组给予等量生理盐水腹腔注射，PDTC干预组给予PDTC100mg／kg一次性腹腔注射；对照组给予生理盐水1ml／kg灌胃后2h，给予等量生理盐水腹腔注射。ELISA法测定大鼠血清IL-1β、TGF-β1、TNF-α及PDGF水平，并分析它们分别与肺脏系数、羟脯氨酸含量的关系；电泳迁移率改变分析法测定肺组织NF—KB活性。结果与对照组比较，染毒组IL-1β含量1、3．7d明显升高，TGF—β1、TNF-α含量各时段均明显升高，PDGF含量7、14、28、56d明显升高，差异均有统计学意义（P〈0．01）；IL-1β、TNF—α分别与肺脏系数成正相关（r=0．37，0．46，P〈O．05或P〈O．01），TGF—β1、PDGF分别与羟脯氨酸含量成正相关（r=0．56，0．89，P〈0．01）；与对照组比较，染毒组肺组织NF—KB活性1、3、7、14d明显升高，差异有统计学意义（P〈0．05或P〈0．01）。与染毒组比较，干预组血清IL-1β、TGF—β1、TNF-β、PDGF含量明显降低，相应时点差异均有统计学意义（P〈0．05或P〈0．01）；肺组织NF—KB活性1、3、7、14d明显降低，差异有统计学意义（P〈0．05或P〈0．01）。结论NF—KB活化及细胞因子IL-1β、TGF-β1、TNF—α、PDGF的过度表达是参与PO致肺损伤的重要机制；PDTC通过抑制NF—KB活化进而抑制上述细胞因子的表达，减轻PQ中毒大鼠的肺损伤。Objective To observe the changes of cytokine and NF-KB activity in acute paraquat poisoned rats and the effect of PDTC and the mechanism of lung injury caused by paraquat poisoning.Methods Sprague-Dawley （SD） rats were randomly divided into three groups： Control group （6 rats）, PQ group （56 rats） and PQ＋PDTC group （46 rats）. On the 1st, the 3rd, the 7th, the 14th, the 28th and the 56th day after treatment, the level of interleukin-I beta （IL-113）, tumor necrosis factor-α （TNF-α, transforming growth factor-1β （TGF-β1） and platelet-derived growth factor （PDGF） in serum were detected; the activity of NF-KB in lung tissues was detected. Results The level of IL-1β increased significantly on the 1st, the 3 rd, the 7th day in PQ group compared with control group （P〈0.01）. The content of TGF-1β and TNF-α in PQ group significantly increased compared with control group （P〈0.05 or P〈0.01）. The level of PDGF significantly increased on the 7th, the 14th, the 28th and the 56th day compared with control group （P〈0.01）. Meanwhile, IL-1β and TNF-α were positively correlated with lung coefficient （r=0.37,0.46 ,P〈0.05 or P〈O.O1 ） ;TGF-1β and PDGF had positive correlation with hydroxyproline （r=0.56,0.89,P〈0.01）. The activity of NF-kB in lung tissue of PQ group significantly increased on the 1st, the 3 rd, the 7th and 14th day compared with control （P〈0.05 or P〈0.01）.There was a significant decrease of IL-1β, TGF-1β TNF-α and PDGF in PQ＋PDTC group compared with PQ group （P〈 0.05 or P〈0.01） in the corresponding sacrifice dates. There was a significant decrease in NF-KB activity on the 1st, the 3rd, the 7th day in PQ＋PDTC group compared with PQ group （P〈0.01）. Conclusion The cytokine and NF-KB could play an important role in lung injury of poisoned rats. PDTC may inhibit the expression of NF-KB and further reduce the production of cytokines, alleviate lung iniury in acute paraquat poisoned rats.

关 键 词：百草枯 NF-KB 细胞因子 急性肺损伤 肺纤维化 

分 类 号：R686[医药卫生—骨科学]