Shi L, Wei M
Department of pharmacy, The fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2017 Sep 20;35(9):663-667. doi: 10.3760/cma.j.issn.1001-9391.2017.09.005.
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) . 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-1mRNA and NF-κB p65mRNA were detected, Statistical analysis were carried out. 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 (=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<0.05) , There were no significant differences in these indicators between control group and PDTC group (>0.05) . 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.
通过观察大鼠核因子（NF-κB）和细胞间黏附分子-1（ICAM-1）的变化以及吡咯烷二硫代氨基甲酸盐（PDTC）的作用，探讨放射性肺损伤所致肺损伤的机制。将80只SD雌性大鼠随机分为4组：对照组、辐射组、PDTC治疗组和PDTC组。采用6 MV X射线建立放射性肺损伤模型，每天照射8 Gy，连续照射5天，每只动物胸部总照射剂量为40 Gy。从照射前3天至首次照射后30天给予PDTC。对照组和PDTC组大鼠给予相同剂量的生理盐水。分别在照射后8周和24周处死动物。取出肺组织进行HE和Masson染色、羟脯氨酸含量测定，并检测实时定量逆转录聚合酶链反应（RT-PCR）ICAM-1mRNA和NF-κB p65mRNA，进行统计学分析。与辐射组相比，PDTC治疗组肺组织病理损伤明显改善。PDTC治疗组肺系数和Hyp含量均显著低于辐射组（分别为3.651、5.293、2.348和4.126，均P<0.05），但略高于对照组。辐射组ICAM-1mRNA和NF-κB p65mRNA水平显著高于PDTC治疗组（均<0.05），对照组和PDTC组这些指标无显著差异（>0.05）。放射性肺损伤大鼠ICAM-1mRNA和NF-κB p65mRNA表达增加。提示ICAM-1和NF-κB是导致放射性肺损伤的关键因素。PDTC可能抑制NF-κB活性，进而显著降低ICAM-1表达，导致肺部炎症和纤维化明显减轻，为放射性肺损伤的防治提供了新的治疗靶点。
