Tmprss6基因对小鼠放射性肠损伤的影响  

Role of Tmprss6 gene in radiation-induced intestinal injury of mice

作　　者：毛久昂 翁震[2] 钮晓音[3] 何杨[2,4] 王振欣[1] MAO Jiu-ang;WENG Zhen;NIU Xiao-yin;HE Yang;WANG Zhen-xin(Department of Oncology,the First Affiliated Hospital of Soochow University,Suzhou 215006,China;MOE Engineering Center of Hematological Disease,Soochow University,Suzhou 215123,China;Shanghai Institute of Immunology,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Jiangsu Institute of Hematology,the First Affiliated Hospital of Soochow University,Suzhou 215006,China)

机构地区：[1]苏州大学附属第一医院肿瘤科,苏州215006 [2]苏州大学血液和血管疾病诊疗药物技术教育部工程研究中心,苏州215123 [3]上海交通大学医学院,上海市免疫学研究所,上海200025 [4]江苏省血液研究所,苏州大学附属第一医院,苏州215006

出　　处：《上海交通大学学报（医学版）》2021年第9期1175-1182,共8页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家自然科学基金(81773356,81871269);上海市卫生和计划生育委员会科研课题(201640137)。

摘　　要：目的·观察Tmprss6基因对小鼠放射性肠损伤的影响。方法·将7~8周龄雄性野生型(WT)小鼠和Tmprss6基因敲除(Tmprss6^(−/−))小鼠各自随机分成未辐照组以及辐照后6 h、24 h、3.5 d和7 d组。其中,辐照组采用11.5 Gy X射线全腹部照射,建立放射肠损伤模型。通过TUNEL染色观察辐照后6、24 h不同肠段隐窝细胞凋亡情况;通过苏木精-伊红染色观察辐照后3.5 d不同肠段病理损伤情况;测量不同肠段辐照前和辐照后3.5、7 d的铁含量,以及抗氧化指标包括超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽(glutathione,GSH)、总抗氧化能力(total antioxidant capacity,T-AOC)和丙二醛(malondialdehyde,MDA),并对铁含量与各项抗氧化指标进行相关性分析。结果·在辐照后3.5 d,Tmprss6^(−/−)和WT小鼠十二指肠绒毛长度均缩短,平均每毫米横截面隐窝计数均减少;Tmprss6^(−/−)小鼠的十二指肠绒毛长度和隐窝计数低于WT小鼠(均P<0.05)。辐照后6、24 h,Tmprss6^(−/−)小鼠十二指肠段每隐窝TUNEL染色阳性细胞数相较于WT小鼠均显著增多(均P<0.05)。而回肠段则相反,辐照后Tmprss6^(−/−)小鼠绒毛长度和隐窝计数显著增加,TUNEL染色阳性细胞数显著减少(均P<0.05)。WT和Tmprss6^(−/−)小鼠十二指肠部位铁含量在辐照后7 d,相较于辐照前均显著升高(均P<0.05);并且Tmprss6^(−/−)小鼠辐照前后的十二指肠铁含量均显著高于同时间点的WT小鼠(均P<0.05)。WT和Tmprss6^(−/−)小鼠辐照后回肠段铁含量较辐照前均升高,其中WT小鼠辐照后3.5 d与辐照前的差异有统计学意义,Tmprss6^(−/−)小鼠辐照后7 d与辐照前的差异有统计学意义(均P<0.05)。辐照后,Tmprss6^(−/−)小鼠十二指肠部位SOD、GSH、T-AOC含量均较WT小鼠低,而MDA含量较高;但只有在辐照后3.5 d的差异具有统计学意义(均P<0.05)。与十二指肠段相反,辐照后Tmprss6^(−/−)小鼠回肠部位SOD、GSH、T-AOC含量较WT小Objective·To explore the effect of Tmprss6 gene on radiation-induced intestinal injury in mice.Methods·7‒8 weeks old wild-type(WT)male mice and Tmprss6 knockout(Tmprss6^(−/−))mice were randomly divided into non-irradiated(IR)group and groups of 6 h,24 h,3.5 d and 7 d post-IR.The IR group received total abdominal X-ray irradiation(TAI)at a dose of 11.5 Gy to establish radiation intestine injury models.H-E staining was performed in the 3.5 d post-IR group,and TUNEL immunofluorescence was performed in the 6 h and 24 h post-IR groups to observe the pathological damage and apoptosis of different intestinal segments,respectively.The levels of iron of different intestinal segments were measured 0,3.5 and 7 d after TAI,as well as superoxide dismutase(SOD),glutathione(GSH),total antioxidant capacity(T-AOC)and malondialdehyde(MDA).The correlation analysis between iron and each antioxidant index was performed.Results·The length of duodenal villi and the number of crypts decreased significantly in both Tmprss6^(−/−)mice and WT mice 3.5 d after TAI.Meanwhile,the duodenal villi length and crypt count of Tmprss6^(−/−)mice were lower than those of WT mice(both P<0.05).The number of TUNEL-positive apoptotic cells per crypt in the duodenal segment of Tmprss6^(−/−)mice was significantly increased compared with that of WT mice 6 and 24 h after TAI(both P<0.05).On the contrary,the length of ileum villi and the count of crypts increased significantly,while the number of TUNEL-positive apoptotic cells decreased significantly in Tmprss6^(−/−)mice compared with that of WT mice(all P<0.05).The iron content in the duodenum of WT and Tmprss6^(−/−)mice 7 d after TAI was significantly increased compared with that of non-irradiated mice(both P<0.05).And the iron content of the duodenum in the Tmprss6^(−/−)mice before and after TAI was significantly higher than that of WT mice at the same time points(all P<0.05).The iron content of the ileum in WT and Tmprss6^(−/−)mice also increased after TAI.And the increa

关 键 词：Tmprss6 放射性肠损伤 铁代谢 氧化应激 

分 类 号：R818[医药卫生—放射医学] R574[医药卫生—临床医学]