Notch信号通路中HIF-1α及Notch-1在组织瓣缺血再灌注损伤后的表达变化  

Expression of HIF-1α and Notch-1 induced by hypoxia after ischemia reperfusion injury in tissue flap

作　　者：李德龙[1] 牛其芳 冯芝恩[1] 苏明[1] 欧阳嘉杰 杨扬[1] 李金忠[1] 徐桥石 韩正学[1] LI De-long;NIU Qi-fang;FENG Zhi-en;SU Ming;OUYANG Jia-jie;YANG Yang;LI Jin-zhong;XU Qiao-shi;HAN Zheng-xue(Department of Oromaxillofacial Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University. Beijing 100050;Department of Stomatology, Fuxing Hospital, Capital Medical University. Beijing 100037, China)

机构地区：[1]首都医科大学附属北京口腔医院口腔颌面-头颈肿瘤科,北京100050 [2]首都医科大学附属复兴医院口腔科,北京100037

出　　处：《中国口腔颌面外科杂志》2018年第3期209-214,共6页China Journal of Oral and Maxillofacial Surgery

基　　金：国家自然科学基金(81570957)

摘　　要：目的 :研究缺氧诱导的Notch信号通路相关因子在组织瓣缺血再灌注损伤后的表达变化,探讨其在组织瓣缺血再灌注损伤后损伤修复中可能的作用。方法:将24只Wistar大鼠随机分为空白对照组(Blank组)、假手术组(Sham组)和实验组(即缺血再灌注损伤组,I/R组),其中空白对照组4只,Sham组4只,I/R组16只。Sham组及I/R组制备大鼠左下腹部4 cm×8 cm皮瓣,I/R组以血管夹夹闭大鼠腹壁浅动、静脉,形成皮瓣缺血状态。Sham组于术后7 d,I/R组分别于去除血管夹(缺血6 h后)即刻及缺血后1、3、7 d过量麻醉处死。利用RT-PCR、Western免疫印迹分析HIF-1α、Notch-1的m RNA扩增水平和蛋白水平。H-E染色观察Sham组及I/R组术后第7天的组织变化。利用SPSS 19.0软件包对数据进行统计学分析。结果:H-E染色结果显示,术后第7天,I/R组较对照组及假手术组可见明显结构紊乱。RT-PCR结果显示,I/R组的HIF-1α、Notch-1 m RNA扩增水平在缺血6 h后即刻及缺血后1、3、7 d均显著高于Sham组及Blank组(P<0.05);Western免疫印迹结果显示,在I/R组,HIF-1α、Notch-1蛋白水平在缺血6 h后即刻及缺血后1、3、7 d均显著高于Sham组及Blank组(P<0.05)。结论:组织瓣在缺血再灌注后,组织出现明显损伤。Notch信号通路在损伤及修复再生过程中被激活,可能与组织缺氧引起的HIF-1α表达升高有关。PURPOSE： To observe the expression of HIF-1α-Notch signaling pathway after ischemic-reperfusion injury.METHODS： Twenty-four Wistar Rats were randomly divided into blank group（4 mice）, sham group（4 mice） and ischemic-reperfusion（I/R） group（16 mice）. The rats of both sham group and IR group were operated to make a 4 cm ×8 cm flap on the left abdomina, then the flaps of IR groups suffered from 6 hours of postoperative ischemia. Four rats were executed each time immediately and the 1 st, the 3 rd, the 7 th day after operation, and the tissue samples in I/R groups were collected. The rats in sham group and blank group were executed at the 7 th day and tissue samples were collected.m RNA expression levels of HIF-1α, Notch-1 were detected by RT-PCR and protein expression levels were detected by Western blot in I/R group, sham group and blank group. The data were analyzed using SPSS 19.0 software package.RESULTS： Histological damage occurred in I/R group at the 7 th day, which was more significantly grave than the sham group and blank group. The expression of HIF-1α, Notch-1 protein in IR group at each time point was significantly higher compared to sham group（P〈0.05）. The expression of HIF-1α, Notch-1 m RNA in IR group at each time point was significantly higher compared to Sham group（P〈0.05）. CONCLUSIONS： Obvious damage of tissue flaps occurred after ischemia and reperfusion. Notch signaling pathway may be activated for tissue repairing and angiogenesis, and it may be induced by high level expression of HIF-1α under tissue hypoxia after ischemia-reperfusion injury.

关 键 词：组织瓣 缺血再灌注损伤 HIF-1Α NOTCH信号通路 缺氧诱导 

分 类 号：R782.2[医药卫生—口腔医学]