摘要目的 观察NF-κB抑制剂氢吡咯二硫代氨基甲酸酯(pyrrolidine dithiocarbamate,PDTC)对放射性肺损伤大鼠肺组织中NF-κBp65mRNA和细胞间黏附分子(intercellular adhesion molecule,ICAM)-1mRNA表达的影响,探讨其对放射性肺损伤的干预作用.方法 将80只Wistar大鼠按随机数字表法分为正常对照组、单纯给药组、单纯照射组和PDTC干预组,每组20只.用全肺连续照射5d,照射剂量为8Gy/d,总剂量为40 Gy.单纯给药组和PDTC干预组照射前3d开始皮下注射PDTC溶剂(10 mg/kg),持续至照射后30 d.正常对照组和单纯照射组大鼠则注射等体积的生理盐水.收集照射后8周和24周时肺组织,行HE和Masson染色观察肺组织病理变化,测定肺湿重并计算肺系数,紫外分光光度计测定羟脯氨酸水平,反转录聚合酶链反应(RT-PCR)检测肺组织ICAM-1和NF-κBp65mRNA表达.结果 24周PDTC干预组大鼠肺组织损伤程度较单纯照射组明显减轻,其肺系数(5.08±0.51)、肺组织羟脯氨酸含量[(0.57±0.05) μg/g]明显低于单纯照射组[肺系数:7.02±1.76和肺组织羟脯氨酸含量:(0.92±0.05)μg/g],差异有统计学意义(P＜0.05);PDTC干预组大鼠肺组织ICAM-1和NF-κBp65mRNA表达分别为:1.04±0.11和0.38±0.08,低于单纯照射组[ICAM-1:1.53±0.17和NF-κBp65mRNA:0.49±0.09],差异有统计学意义(均P＜0.05).结论 放射性肺损伤大鼠肺组织ICAM-1mRNA和NF-κBp65mRNA表达增高,提示ICAM-1和NF-κB的过度表达可能是放射性肺损伤发病的重要因素;PDTC通过抑制NF-κB的活化调控ICAM-1的表达,减轻肺部炎症和纤维化,可能为放射性肺损伤的预防和治疗提供新的靶点.

abstractsObjective To investigate the mechanism of lung injury caused by radiation-induced lung injury by observing the change of nuclear factor (NF-κB) and intercellular adhesion moceule-1 (ICAM-1) in rats and the effects of pyrrolidine dithiocarbamate (PDTC).Methods 80 SD female rats were randomly classified into 4 groups:control group,radiation group,PDTC treatment group and PDTC group.The radiation induced pulmonary injury model was preformed by using 6 MV X-rays to deliver 8 Gy per day for 5 consecutive days with 40 Gy in total to the thorax of each animal.PDTC was given from 3 d before radiation to 30 d after the first radiation.Rats in control group and PDTC group received the same dose of saline.Animals were sacrificed at 8 week and 24 week after radiation,respectively.The lungs were removed and processed for HE and Masson staining,hydroxyproline content measurement,and real-time quantitative reverse transcription-polymerase chain(RT-PCR) ICAM-1 mRNA and NF-κB p65mRNA were detected,Statistical analysis were carried out.Results Compared with radiation group,there was an obvious amelioration in pathological injury of lung tissue in PDTC treatment group.The lung coefficient and the content of Hyp in PDTC treatment group were significantly lower than those in radiation group (t =3.651,5.293,2.348 and 4.126,respectively,allP ＜0.05),while slightly higher than those in control group.The levels of ICAM-1mRNA and NF-κB p65mRNA were significantly higher in radiation group than that in PDTC treatment group (all P＜0.05),There were no significant differences in these indicators between control group and PDTC group (P＞0.05).Conclusion The expression of ICAM-1mRNA and NF-κB p65mRNA is increased in rats with radiation-induced lung injury.Suggest that ICAM-1 and NF-κB are a key factor lead to radiation-induced lung injury.PDTC may inhibits NF-κB activity and further significantly deceases expression of ICAM-1,leading to significantly attenuated pulmonary inflammation and fibrosis,which provides a new therapeutic target for the prevention and treatment of radiation-induced lung injury.