慢病毒介导SIRT6过表达对大鼠放射性肺损伤保护作用的实验研究
Experimental study on the protective effect of lentivirus-mediated SIRT6 overexpression on radioactive lung injury in rats
王季颖 1盛兆瑛 1蔡勇2
作者信息
- 1. 同济大学附属上海肺科医院 肿瘤科,上海 200433
- 2. 同济大学附属上海市肺科医院 放疗科,上海 200433
- 折叠
摘要
目的 探讨慢病毒介导沉默信息调节蛋白6(SIRT6)过表达对大鼠放射性肺损伤的保护作用.方法 72只雄性150～200 g Wistar大鼠随机分为3组(n=24),采用6 MV-X线直线加速器照射双肺造模,各组分别在造模当天尾静脉注射生理盐水(对照组和单纯照射组)和携带过表达SIRT6的慢病毒(Lent-SIRT6组),分别在放射1周、2周、4周、8周后检测呼吸频率及血清中的肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)水平,放射8周后处死大鼠留取肺组织,HE染色评估肺组织病理学改变,ELISA法检测肝组织中TNF-α、IL-6和IL-1β水平.结果 对照组的肺泡壁、肺泡间质等肺组织结构正常,而单纯照射组的肺泡壁明显增厚且纤维化,肺泡间质可见大量的增生纤维组织,Lent-SIRT6组大鼠肺泡壁增厚及肺泡间质纤维化症状较单纯照射组减轻.与对照组相比,单纯照射组放射后的呼吸频率、血清TNF-α和IL-6水平、中性粒细胞计数及肝组织TNF-α、IL-6和IL-1β水平均升高,白细胞和淋巴细胞计数均降低,差异有统计学意义(P＜0.05);过表达SIRT6的慢病毒可缓解放射导致的以上指标异常(P＜0.05).结论 SIRT6可有效抑制炎症反应,减轻放射线肺炎肺损伤症状,对肺损伤有一定的保护和防治作用.
Abstract
Objective To investigate the protective effect of lentivirus-mediated silencing information regulation protein 6(SIRT6)overexpression on radioactive lung injury in rats.Methods 72 male 150-200 g Wistar rats were randomly divided into three groups(n=24).The 6 MV-X-ray linear accelerator was used to irradiate the lungs.The rats in each group were injected with normal saline(TNF-α)were measured at 1, 2, 4, and 8 weeks after radiotherapy(Lent-SIRT6), and the levels of tumor necrosis factor-α(TNF-IL-6 and IL-1β were measured by HE staining.The levels of TNF-α, IL-6 and IL-1β in liver tissue were detected by HE staining.The levels of TNF-α, IL-6 and IL-1β in liver tissue were detected by HE staining.Results The alveolar wall and alveolar stroma were normal in the control group.The alveolar wall of the irradiated group was thickened and fibrosis, and a large number of hypertrophic fibrous tissues were found in the alveolar stroma.The alveolar wall of Lent-SIRT6 group was thickened And alveolar stromal fibrosis symptoms were lighter than the irradiation group.Compared with the control group, the levels of serum TNF-α and IL-6, neutrophil count and the levels of TNF-α, IL-6 and IL-1β in the liver tissue were significantly higher than those in the control group (P<0.05).The lentiviruses overexpressing SIRT6 could alleviate the abnormalities caused by radiation (P<0.05).The difference was statistically significant (P<0.05).Conclusion SIRT6 can effectively inhibit the inflammatory reaction, reduce the lung injury symptoms of radiation pneumonia, and have some protective and prevention effect on lung injury.
关键词
沉默信息调节蛋白6/放射性肺炎/肺损伤/炎症Key words
silencing information regulating protein 6/radiation pneumonia/lung injury/inflammation引用本文复制引用
基金项目
上海市科学技术委员会科研计划项目(15ZR1434300)
出版年
2017
NETL
NSTL
维普
万方数据