核因子-κB及细胞因子在百草枯致大鼠肺损伤中的动态变化

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-β1(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-kappa B(NF-κB)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.染毒组和十预组给予生理盐水稀释PQ80 mg/kg一次性灌胃后2 h,染毒组给予等量生理盐水腹腔注射,PDTC干预组给予PDTC 100 mg/kg一次性腹腔注射;对照组给予生理盐水1 ml/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-κB活性.结果 与对照组比较,染毒组IL-1β含量1、3、7 d明显升高,TGF-β1、TNF-α含量各时段均明显升高,PDGF含量7、14、28、5 6d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<0.05或P<0.01),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、14 d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-α、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-κB活性1、3、7、14 d明显降低,差异有统计学意义(P<0.05或P<0.01).结论 NF-κB活化及细胞因子IL-1β、TGF-β1、TNF-α、PDGF的过度表达是参与PQ致肺损伤的重要机制;PDTC通过抑制NF-κB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.

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

Objective To observe the changes of cytokine and NF-κB 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-1β), tumor necrosis factor-or (TNF-α), transforming growth factor-β1(TGF-β1)and platelet-derived growth factor (PDGF) in serum were detected; the activity of NF-κB 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-β1 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<0.01) ;TGF-β1 and PDGF had positive correlation with hydroxyproline (r=0.56,0.89,P<0.01). The activity of NF-κB 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-β1, 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-κB 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-κB could play an important role in lung injury of poisoned rats. PDTC may inhibit the expression of NF-κB and further reduce the production of cytokines, alleviate lung injury in acute paraquat poisoned rats.