摘要
目的:本文探索多次X射线放射导致大鼠放射性肺炎(radiation pneumonitis,RP)模型条件,并采用多指标进行模型评价,优化建立一种快速、稳定的放射性肺炎造模条件。方法:采用不同强度X射线对大鼠胸部进行照射,检测大鼠无创性肺功能指标后,取肺组织观察病理改变,结合动物肺功能、病理变化及死亡率筛选照射条件。筛选出较为合适的照射条件进行照射造模,采用酶联免疫法检测造模后2、4、6、8 w各个时期的大鼠血清及肺组织的肿瘤坏死因子α(TNF-α)、白介素6(IL-6)和转化生长因子β1(TGF-β1)含量;HE染色观察各造模时长的肺组织损伤的病理变化,探索照射后模型发展规律。结果:采用40、50 Gy X射线照射,8 w后动物肺功能均明显降低(P<0.05或P<0.01),两组均出现较为典型的放射性肺炎病理变化,但结合50 Gy造模组出现较多动物死亡情况,选择40 Gy的照射强度较为合适。采用40 Gy强度进行照射,照射后6~8 w为良好的炎症发作时期,此期间血清及肺组织中TNF-α、IL-6含量明显升高(P<0.05或P<0.01),所有动物肺组织病理均发生显著改变。结论:采用40 Gy的X射线照射强度可建立快速、稳定的放射性肺炎模型,照射后6~8 w可作为反映药物作用的给药周期,本研究为RP的稳定可靠模型。
Objective:To explore the modeling conditions of radiation pneumonitis(RP)induced by multiple X-ray radiation and employ multiple indexes for model evaluation,thus establishing a rapid and stable modeling method for RP.Methods:The rat chest was irradiated by X-ray with different intensities,and after non-invasive determination of lung function indexes,the lung tissue was collected for observation of pathological changes.Then,exposure conditions were screened according to the lung function,pathological changes,and mortality of rats,and the suitable conditions were selected for modeling.The enzyme-linked immunosorbent assay was employed to measure the levels of inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and transforming growth factor-β1(TGF-β1)]in the serum and lung tissue of rats 2,4,6,and 8 weeks after modeling.Hematoxylin-eosin staining was performed to observe the pathological changes in the lung tissue and explore the development law of the model after irradiation.Results:Eight weeks after X-ray irradiation at 40 Gy and 50 Gy,the rats showed significantly compromised lung function and typical pathological changes of RP.However,considering that more rats died in the 50 Gy group,the radiation intensity of 40 Gy was more appropriate.The radiation intensity of 40 Gy was then used for modeling,and 6-8 weeks after irradiation was a good inflammatory period,with elevated levels of TNF-αand IL-6 in the serum and lung tissue(P<0.01 or P<0.05).All rats showed significant pathological changes in the lung tissue.Conclusion:The X-ray irradiation intensity of 40 Gy can be used to rapidly establish a stable animal model of RP,and 6-8 weeks after irradiation can be used as the drug administration cycle reflecting the effects of drugs.This study provides reference for establishing a stable and reliable model of RP.
作者
刘梦娇
李晓岑
贠亚波
赵玉培
李艳英
任钧国
刘建勋
LIU Mengjiao;LI Xiaocen;YUN Yabo;ZHAO Yupei;LI Yanying;REN Junguo;LIU Jianxun(Beijing Increase Innovative Medicine Co.,Ltd.,Beijing 102200;Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine,Institute of Basic Medical Sciences,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091;Beijing Increasepharm Safety and Efficacy Co.,Ltd.,Beijing 102200)
出处
《中药药理与临床》
北大核心
2025年第10期71-75,共5页
Pharmacology and Clinics of Chinese Materia Medica
基金
中关村开放实验室成果转化概念验证项目(编号:20220481093)。
