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

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。

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-6and 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.