摘要
目的观察急性百草枯(PQ)中毒大鼠肺组织中p38丝裂原活化蛋白激酶(p38MAPK)及核因子-κB(NF-κB)的变化,探讨褪黑素(MT)的治疗效果。方法将128只SD大鼠随机分为染毒组60只、治疗组60只和对照组8只,对染毒组以生理盐水稀释PQ 50 mg/kg,一次性灌胃;治疗组PQ灌胃后的大鼠以MT 10mg/kg腹腔注射,每日1次;对照组生理盐水一次性灌胃。于不同处理后1、3、7及14 d时分别测定大鼠血清中丙二醛(MDA)含量;电泳迁移率改变分析法(EMSA)检测大鼠肺组织中NF-κB活性;Western blot检测磷酸化p38MAPK蛋白水平,同时观察大鼠肺组织病理变化。结果染毒组大鼠血清MDA浓度在1、3及7 d分别为(4.45±1.23)、(3.77±1.12)及(2.84±0.96)nmol/ml,较对照组明显升高,差异有统计学意义(P<0.01);治疗组MDA浓度1、3及7 d分别为(2.68±0.85)、(1.97±0.74)和(1.53±0.62)nmol/ml,较染毒组明显降低,差异有统计学意义(P<0.05)。染毒组大鼠肺组织磷酸化p38MAPK蛋白水平及NF-κB活性在各时间点均明显高于对照组,差异有统计学意义(P<0.01)。经MT治疗后磷酸化p38MAPK蛋白水平及NF-κB活性均明显降低,差异有统计学意义(P<0.05)。治疗组大鼠肺组织病理改变较染毒组明显减轻。结论磷酸化p38MAPK及NF-κB活性在百草枯所致大鼠肺组织中明显增高;MT能降低磷酸化p38MAPK蛋白水平,抑制NF-κB的活化,减轻染毒大鼠肺组织损伤。
Objective To investigate NF-κB activity and the expression of phosphorylated p38MAPK protein in lung tissue of acute paraquat poisoned rats and the effect of MT. Methods One hundred and twenty-eight Sprague-Dawley （SD） rats were randomly divided into three experimental groups： poisoned group, MT group and control group. On the 1st, the 3rd, the 7th and the 14th day after exposure,levels of malondialdehyde （MDA） in serum were detected; NF-κB activity in the lung tissues was assessed by electrophoresis mobility shift assay （EMSA）; the expression of the phosphorylated p38MAPK was evaluated by Western blot method; the lung pathological changes of rats were observed. Results The level of malondialdehyde （MDA） in serum increased significantly in poisoned group on the 1st day （4.45±1.23）,the 3rd day （3.77±1.12） and the 7th day （2.84±0.96）nmol/ml compared with that in control group （1.36±0.52）nmol/ml （P〈0.01）. There was a significant decrease in MT group on the 1st day （2.68±0.85）,the 3rd day （1.97±0.74） and the 7th day （1.53±0.62）nmol/ml compared with poisoned group （P〈0.05）. The expression of the phosphorylated p38MAPK and NF-κB activity in lung tissue of poisoned group significantly increased compared with control group （P〈0.01）. There was a significant decrease in NF-κB activity and expression of the phosphorylated p38MAPK in the lung tissues in MT group compared with poisoned group （P〈0.05）. Conclusion NF-κB and p38MAPK could play an important role in lung injury of poisoned rats. MT may inhibit the expression of NF-κB and phosphorylated p38MAPK, and therefore might have the therapeutical effect on acute paraquat poisoning.
出处
《中华劳动卫生职业病杂志》
CAS
CSCD
北大核心
2007年第9期518-522,共5页
Chinese Journal of Industrial Hygiene and Occupational Diseases
基金
省科技攻关项目(052761501)
