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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 observe the changes of p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-κB (NF-κB) in lung tissue of acute paraquat (PQ) poisoned rats and to explore the therapeutic effect of melatonin (MT). Methods 128 Sprague-Dawley rats were randomly divided into two groups: 60 rats in the treatment group, 60 rats in the treatment group and 8 rats in the control group. The rats in the exposure group were treated with PQ 50 mg / kg in physiological saline, The rats were injected intraperitoneally with MT 10 mg / kg once a day, and the control group received normal saline once a day. The contents of malondialdehyde (MDA) in rat serum were determined at 1, 3, 7 and 14 days after treatment respectively. The activity of NF-κB in lung tissue was detected by electrophoretic mobility shift assay (EMSA) Phosphorylation p38MAPK protein levels, while observing the pathological changes of lung tissue in rats. Results Compared with the control group, the concentration of serum MDA in the exposed group was (4.45 ± 1.23), (3.77 ± 1.12) and (2.84 ± 0.96) nmol / ml on the 1st and 7th day, respectively, (2.68 ± 0.85), (1.97 ± 0.74) and (1.53 ± 0.62) nmol / ml respectively, which were significantly lower than those in the control group (P <0.01) Significance (P <0.05). The levels of phosphorylated p38MAPK protein and NF-κB in the lung tissue of rats in the exposure group were significantly higher than those in the control group at each time point (P <0.01). After MT treatment phosphorylated p38MAPK protein levels and NF-κB activity were significantly lower, the difference was statistically significant (P <0.05). The pathological changes of lung tissue in the treatment group were significantly reduced than those in the treated group. Conclusion The phosphorylation of p38MAPK and NF-κB in lung tissue of rats induced by paraquat were significantly increased. MT decreased the protein level of phosphorylated p38MAPK, inhibited the activation of NF-κB and attenuated the lung injury in rats.