文献类型：期刊文献

中文题名：归芪益元膏对12C^(6+)束辐射旁效应肺损伤大鼠的保护作用及其机制

英文题名：Effect and mechanism of Guiqi Yiyuan ointment on rats injured by side effect of 12C^(6+) beam radiation

作者：马天星[1];李金田[1,2];李娟[3];张毅[1];梁建庆[2,3];古常军[1];张悦[1]

第一作者：马天星

机构：[1]甘肃中医药大学中医临床学院,兰州730101;[2]敦煌医学与转化教育部重点实验室,兰州730000;[3]甘肃中医药大学基础医学院,兰州730101

第一机构：甘肃中医药大学中医临床学院

年份：2021

卷号：46

期号：9

起止页码：876

中文期刊名：解放军医学杂志

外文期刊名：Medical Journal of Chinese People's Liberation Army

收录：CSTPCD;;Scopus;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金(81460695);中国博士后科学基金(2016M602887);甘肃省中医药研究中心开放课题(zyzx-2020-zx17)

语种：中文

中文关键词：辐射旁效应;肺损伤;归芪益元膏;12C^(6+)束辐射;转化生长因子-β1;Smad蛋白

外文关键词：radiation-induced bystander effect;lung injuries;Guiqi Yiyuan ointment;12C^(6+)beam radiation;transforming growth factor-β1;Smad protein

摘要：目的探讨归芪益元膏对12C^(6+)束辐射旁效应(RIBE)肺损伤大鼠的作用及可能机制。方法70只Wistar雄性大鼠随机分为空白对照组、辐射24 h组、归芪益元膏+辐射24 h组、归芪益元膏24 h组、辐射7 d组、归芪益元膏+辐射7 d组、归芪益元膏7 d组,每组10只。各归芪益元膏组和归芪益元膏+辐射组照射前14d给予归芪益元膏灌胃,空白对照组和各辐射组灌胃等量生理盐水。14 d后,各辐射组及归芪益元膏+辐射组大鼠右肺予4 Gy 12C^(6+)束单次照射(仅暴露右肺部位),空白对照组与各归芪益元膏组不照射,照射后持续灌胃给药至24 h、7 d时间点处死大鼠,收集双肺组织,HE染色观察左右肺组织病理学变化,Q-PCR检测左右肺组织中转化生长因子-β1(TGF-β1)、p-Smad3 mRNA表达水平,Western blotting检测左右肺组织中TGF-β1、p-Smad3、Smad6蛋白表达水平。结果HE染色结果显示,空白对照组及各归芪益元膏组双肺肺泡结构正常。辐射24 h组双肺肺泡间隔增大,炎性细胞浸润。归芪益元膏+辐射24 h组双肺部分肺泡间隔断裂,部分炎性细胞浸润。辐射7 d组肺泡间隔断裂明显,肺泡腔不规则扩大,炎性细胞浸润,左肺浸润程度较右肺轻。归芪益元膏+辐射7 d组无纤维增生,肺泡腔内无充血,左肺损伤程度较右肺轻。Q-PCR和Western blotting检测结果显示,与空白对照组比较,辐射24 h组和辐射7 d组大鼠左右肺组织中TGF-β1 mRNA和蛋白表达水平均升高(P<0.05),p-Smad3蛋白表达水平升高(P<0.05),右肺Smad6 mRNA表达水平降低(P<0.05),左肺Smad6 mRNA表达水平升高(P<0.05),左右肺组织中Smad6蛋白表达水平降低(P<0.05),且辐射7 d组大鼠左右肺组织中TGF-β1 mRNA和蛋白表达水平高于辐射24 h组(P<0.05),存在时间效应。与相同时间点辐射组比较,各归芪益元膏+辐射组大鼠左右肺组织中TGF-β1 mRNA和蛋白、p-Smad3蛋白表达水平降低,Smad6 mRNA和蛋白表达水平升高,差异有统计学意义(P<0.05)。结论归芪益元膏对辐射旁效应肺损伤大鼠具有防护作用,其机制可能与下调肺组织中TGF-β1、p-Smad3 mRNA和蛋白的表达,上调Smad6 mRNA和蛋白的表达有关。
Objective To explore the effect and potential mechanism of Guiqi Yiyuan ointment on rats injured by bystander effects of 12C6+radiation.Methods A total of 70 Wistar male rats were randomized into the following groups(n=10):blank control group,radiation 24 h group,Guiqi Yiyuan ointment+radiation 24 h group,Guiqi Yiyuan ointment 24 h group,radiation 7 d group,Guiqi Yiyuan ointment+radiation 7 d group,and Guiqi Yiyuan ointment 7 d group.Fourteen days before irradiation,rats in the groups with Guiqi Yiyuan ointment treatment received the same volume and concentration of Guiqi Yiyuan ointment.Other rats received the same amount of normal saline.After 14 days,the right lungs of each radiation group and the Guiqi Yiyuan ointment+radiation group were irradiated with a single 4 Gy 12C^(6+)beam(exposing only the right lung).The blank control group and each Guiqi Yiyuan ointment group were not irradiated.Rats in each group were sacrificed at different time points such as 24 h and 7 d,and lung tissues were collected.The histology of the left and right lungs of each group was examined by HE staining.The mRNA and protein expression levels of TGF-β1 and p-Smad3 in the left and right lung tissues were quantified by Q-PCR and Western blotting,respectively.Results HE staining results showed the normal structure of the right lung alveoli of blank control group and each Guiqi Yiyuan ointment group.In radiation 24 h group,the alveolar septum of both lungs increased with inflammatory cells infiltrated.In Guiqi Yiyuan ointment+radiation 24 h group,both lungs showed some broken alveolar septum and some infiltrated inflammatory cells.In radiation 7 d group,the alveolar septal fissure was obvious,the alveolar cavity expanded irregularly,the inflammatory cells infiltrated,and the degree of infiltration in the left lung was lighter than that in the right lung.In Guiqi Yiyuan ointment+radiation 7 d group,there was no fibrous hyperplasia,no congestion in the alveolar cavity,and the degree of left lung injury was lighter than that of the right lung.Q-PCR and Western blotting results showed that compared with blank control group,the expression levels of TGF-β1 mRNA and protein in the left and right lung tissues of rats in radiation 24 h group and radiation 7 d group increased(P<0.05),the expression level of p-Smad3 protein increased(P<0.05),the expression level of Smad6 mRNA in the right lung decreased(P<0.05),and the expression level of Smad6 mRNA in the left lung increased(P<0.05),the expression of Smad6 protein decreased in the left and right lung tissues(P<0.05),and the expressions of TGF-β1 mRNA and protein in radiation 7 d group were higher than those in radiation 24 h group(P<0.05),and there was a time effect.The expressions of TGF-β1 mRNA and protein and p-Smad3 protein in the left and right lungs of rats in Guiqi Yiyuan ointment+radiation group decreased,while the expression of Smad6 mRNA and protein increased(P<0.05).Conclusion Guiqi Yiyuan ointment has a protective effect on rats with bystander effects of radiation.The mechanism may be related to the downregulation of TGF-β1 and p-Smad3,but increased Smad6 in the left and right lung tissues.