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

doi:10.19438/j.cjoms.2018.03.004

中国口腔颌面外科杂志 ›› 2018, Vol. 16 ›› Issue (3): 209-214.doi: 10.19438/j.cjoms.2018.03.004

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

李德龙¹，牛其芳²，冯芝恩¹，苏明¹，欧阳嘉杰¹，杨扬¹，李金忠¹，徐桥石¹，韩正学¹

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

收稿日期:2017-12-04 修回日期:2018-01-23 出版日期:2018-05-20 发布日期:2018-06-12
通讯作者: 韩正学，E-mail：hanf1989@126.com
作者简介:李德龙（1989-），男，硕士研究生，住院医师，E-mail：ldl11000@126.com
基金资助:
国家自然科学基金（81570957）

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

LI De-long¹, NIU Qi-fang², FENG Zhi-en¹, SU Ming¹, OUYANG Jia-jie¹, YANG Yang¹, LI Jin-zhong¹, XU Qiao-shi¹, HAN Zheng-xue¹.

1.Department of Oromaxillofacial Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University. Beijing 100050;
2.Department of Stomatology, Fuxing Hospital, Capital Medical University. Beijing 100037, China

Received:2017-12-04 Revised:2018-01-23 Online:2018-05-20 Published:2018-06-12

摘要/Abstract

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mRNA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 mRNA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。

关键词: 组织瓣, 缺血再灌注损伤, HIF-1α, Notch 信号通路, 缺氧诱导

Abstract: 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 4cm×8cm 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 1st, the 3rd , the 7th 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 7th day and tissue samples were collected. mRNA 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 7th 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 mRNA 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.

Key words: Tissue flap, Ischemia-reperfusion injury, HIF-1α, Notch signaling pathway, Hypoxia

中图分类号:

R782.2

李德龙，牛其芳，冯芝恩，苏明，欧阳嘉杰，杨扬，李金忠，徐桥石，韩正学. 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[J]. 中国口腔颌面外科杂志, 2018, 16(3): 209-214.

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.. Expression of HIF-1α and Notch-1 induced by hypoxia after ischemia reperfusion injury in tissue flap[J]. China J Oral Maxillofac Surg, 2018, 16(3): 209-214.

参考文献

[1] 韩正学, 李华, 李金忠, 等. 口腔颌面缺损游离组织移植修复138例临床分析 [J]. 北京口腔医学, 2010, 18(4): 225-227.
[2] 韩正学, 李金忠, 李华, 等. 游离组织瓣移植重建颅内外沟通性缺损的临床研究 [J]. 中华神经外科杂志, 2012, 28(8): 772-774.
[3] Schmidt Y, Bannasch H, Eisenhardt SU. Ischemia-reperfusion injury leads to significant tissue damage in free flap surgery [J]. Plast Reconstr Surg, 2012, 129(1): 174e-175e, 175e-176e.
[4] van den Heuvel MG, Buurman WA, Bast A, et al. Review: Ischaemia-reperfusion injury in flap surgery [J]. J Plast Reconstr Aesthet Surg, 2009, 62(6): 721-726.
[5] Ramasamy SK, Kusumbe AP, Wang L, et al. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone [J]. Nature, 2014, 507(7492): 376-380.
[6] Park ST, Kim BR, Park SH, et al. Suppression of VEGF expression through interruption of the HIF1alpha and Akt signaling cascade modulates the antiangiogenic activity of DAPK in ovarian carcinoma cells [J]. Oncol Rep, 2014, 31(2): 1021-1029.
[7] Du S, Wang S, Wu Q, et al. Decorin inhibits angiogenic potential of choroid-retinal endothelial cells by downregulating hypoxia-induced Met, Rac1, HIF-1alpha and VEGF expression in cocultured retinal pigment epithelial cells [J]. Exp Eye Res, 2013, 116: 151-160.
[8] Cury V, Moretti AI, Assis L, et al. Low level laser therapy increases angiogenesis in a model of ischemic skin flap in rats mediated by VEGF, HIF-1α and MMP-2 [J]. J Photochem Photobiol B, 2013, 125: 164-170.
[9] 欧阳嘉杰, 李德龙, 韩正学, 等. 游离组织瓣缺血再灌注损伤实验动物模型的建立 [J]. 北京口腔医学, 2016, 24(1): 10-13.
[10] 欧阳嘉杰, 苏明, 李德龙, 等. 硝酸盐转运蛋白Sialin与游离组织瓣缺血再灌注损伤的相关性研究[J]. 中华显微外科杂志, 2017, 40(3): 252-256.
[11] Wacker A, Gerhardt H, Phng LK. Tissue guidance without filopodia [J]. Commun Integr Biol, 2014, 7: e28820.
[12] Hellstr?m M, Phng LK, Hofmann JJ, et al. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis [J]. Nature, 2007, 445(7129): 776-780.
[13] Shutter JR, Scully S, Fan W, et al. Dll4, a novel Notch ligand expressed in arterial endothelium [J]. Genes Dev, 2000, 14(11): 1313-1318.
[14] Ahluwalia A, Jones MK, Tarnawski AS. Key role of endothelial importin-alpha in VEGF expression and gastric angiogenesis: novel insight into aging gastropathy [J]. Am J Physiol Gastrointest Liver Physiol, 2014, 306(4): G338-G345.
[15] Liu R, Trindade A, Sun Z, et al. Inhibition of Notch signaling by Dll4-Fc promotes reperfusion of acutely ischemic tissues [J]. Biochem Biophys Res Commun, 2012, 418(1): 173-179.
[16] Ojamaa K. Signaling mechanisms in thyroid hormone-induced cardiac hypertrophy [J]. Vascul Pharmacol, 2010, 52(3-4): 113-119.
[17] Sadat U. Signaling pathways of cardioprotective ischemic preconditioning [J]. Int J Surg, 2009, 7(6): 490-498.

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

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 9

编辑推荐

Metrics

本文评价

[1]	李曼容, 娄雅静. Orem自理模式在90例口腔鳞癌患者游离组织瓣移植术后的应用价值评价[J]. 中国口腔颌面外科杂志, 2021, 19(6): 553-556.
[2]	江灿洋, 施斌, 黄建平, 江燕, 朱小峰, 黄立, 林李嵩. 游离血管化复合组织瓣在口腔颌面部严重创伤性缺损畸形整复中的应用：11例临床分析[J]. 中国口腔颌面外科杂志, 2020, 18(2): 155-159.
[3]	牛其芳, 李德龙, 杨杨, 秦力铮, 冯芝恩, 李金忠, 韩正学. 人血管内皮细胞缺氧复氧损伤细胞模型的建立[J]. 中国口腔颌面外科杂志, 2019, 17(4): 295-299.
[4]	吴忆来, 王国民, 杨育生, 万腾, 陈阳, 梁赟. 咽后壁组织瓣转移术后渗血的原因分析和处理[J]. 中国口腔颌面外科杂志, 2019, 17(2): 171-174.
[5]	王耀钟, 杨银辉, 官群立, 林锡江. 应用上唇动脉逆行血供邻近瓣和Bernard-Webster颊部推进组织瓣修复巨大下唇癌切除术后缺损：1例报告及文献复习[J]. 中国口腔颌面外科杂志, 2019, 17(1): 93-96.
[6]	唐渔, 曹巍, 彭灿邦, 刘喆麒, 林承重, 季彤. 缺氧诱导因子1α在成釉细胞瘤中的表达及意义[J]. 中国口腔颌面外科杂志, 2018, 16(4): 343-347.
[7]	羊良慧，麦华明，巫家晓，李帅，陈国生，刘诗奇. 血清生化因素与口腔颌面部游离组织瓣血管危象的相关分析[J]. 中国口腔颌面外科杂志, 2017, 15(5): 431-434.
[8]	尹长伟，吴海威，黄圣运，马猛，陈占伟，张东升,. 二氯化钴诱导唾液腺腺样囊性癌ACC-M细胞自噬的实验研究[J]. 中国口腔颌面外科杂志, 2015, 13(6): 491-496.
[9]	沈佩;霍亮;张善勇;杨驰;恽白. 颞下颌关节盘锚固术中脂肪组织瓣转归的实验研究 [J]. 中国口腔颌面外科杂志, 2013, 11(5): 377-381.