归芪益元膏对重离子辐射旁效应损伤大鼠的影响

张朝宁 李金田 刘永琦 蔺兴遥 李雪燕 孙少伯 李娟 王萌 陈继尧

摘要：目的 觀察归芪益元膏对重离子辐射旁效应损伤大鼠的影响，探讨其可能的作用机制。方法 将42只SPF级Wistar雄性大鼠随机分为空白对照组、单纯辐射组和归芪益元膏组。归芪益元膏组预先给予归芪益元膏灌胃2周，单纯辐射组和归芪益元膏组大鼠右肺予2 Gy 12C6+离子束单次照射，空白对照组不予照射。照射后6、12、24 h处死各组大鼠，检测外周血象及白细胞介素（IL）-6、转化生长因子-β1（TGF-β1）、IL-1β含量，HE染色观察大鼠肺组织病理形态。结果 与空白对照组比较，照射后12 h单纯辐射组大鼠血清IL-6、TGF-β1、IL-1β含量明显升高（P<0.01），外周血白细胞、红细胞、血小板、血红蛋白明显下降（P<0.01）；HE染色显示照射后24 h大鼠肺泡壁增厚，肺泡腔内有渗出物及炎性细胞浸润等病理改变。与单纯辐射组12 h比较，归芪益元膏组12 h大鼠IL-6、TGF-β1、IL-1β含量明显下降（P<0.01），血常规各项指标显著上升（P<0.01），大鼠肺组织病理损伤有一定的改善。结论 归芪益元膏对重离子辐射旁效应损伤具有防护作用。

关键词：辐射旁效应；重离子；归芪益元膏；转化生长因子-β1；白细胞介素-6；白细胞介素-1β；大鼠；雄性

DOI：10.3969/j.issn.1005-5304.2017.07.011

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2017）07-0045-04

Abstract： Objective To discuss the protective effects of Guiqi Yiyuan Ointment on damages caused by heavy ion radiation induced bystander effects； To explore the possible mechanism. Methods Totally 42 Wistar male rats were randomly divided into blank control group， pure radiation group and Guiqi Yiyuan Ointment group. The Guiqi Yiyuan Ointment group was given Guiqi Yiyuan Ointment by gavage for two weeks in advance. Later the right lungs of the rats in the pure radiation group and Guiqi Yiyuan Ointment group were radiated once by 2 Gy 12C6+， while the blank control group received no radiation. 6， 12， 24 h after radiation all groups of rats were executed. Peripheral hemogram and the levels of IL-6， TGF-β1 and IL-1β in serum of the rats were examined. The changes of lung tissue pathology morphology in the rats were observed by HE staining. Results Compared with the blank control group， the contents of IL-6， TGF-β1 and IL-1β in serum of the pure radiation group increased obviously at 12 h after radiation （P<0.01）， and the amount of leukocyte， erythrocyte， blood platelet and hemoglobin distinctly declined at 12 h after radiation （P<0.01）； HE staining showed that the alveolar wall was thickened at 24 h after radiation， and there were exudate and inflammatory cell infiltration in the alveolar cavity. Compare with the pure radiation group at 12 h after radiation， the levels of IL-6， TGF-β1 and IL-1β in Guiqi Yiyuan Ointment group decreased significantly at 12 h after radiation （P<0.01）. Indexes of blood routine significantly increased （P<0.01）， and the pathological changes of lung tissue in rats improved （P<0.01）. Conclusion Guiqi Yiyuan Ointment can protect damages caused by heavy ion radiation induced bystander effects.

Key words： radiation induced bystander effects； heavy ion； Guiqi Yiyuan Ointment； TGF-β1； IL-6； IL-1β； rats； male

恶性肿瘤是威胁人类健康的主要疾病，放疗是治疗恶性肿瘤的重要手段之一。重离子因具有高线性传

能密度、高能量沉积峰、相对高的生物学效应等优点，成为理想的肿瘤放疗用射线[1-2]，但重离子放疗时也会对周围健康组织产生间接损伤，即辐射旁效应。辐射旁效应的机制目前尚未完全研究清楚，其防护是辐射生物学和临床放疗治癌领域的重要研究内容。中药因高效、低毒、防治结合等优点成为目前辐射防护剂的研究热点[3]。归芪益元膏源自清·程国彭《医学心悟》黄芪汤，加甘肃道地药材当归而成，全方具有益气滋阴、补肺益肾、养血活血的功效。本实验用归芪益元膏对重离子辐射旁效应损伤大鼠预先干预，观察其对重离子辐射旁效应的防护作用，并探讨其可能的作用机制。……