中性粒细胞明胶酶相关脂质运载蛋白(NGAL)信号通路在猪静脉桥血管早期再狭窄模型中的表达及作用  

Expression and role of neutrophil gelatinase-associated lipocalin(NGAL) signaling pathways in the early stage of vein graft restenosis of a pig model

作　　者：尹力[1] 陈文[1] 何帅[1] 邱志兵[1] YIN Li;CHEN Wen;HE Shuai;QIU Zhibing(Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210000, P.R.China)

机构地区：[1]南京医科大学附属南京医院南京市第一医院心胸血管外科,南京210000

出　　处：《中国胸心血管外科临床杂志》2018年第5期427-433,共7页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

基　　金：江苏省省级重点研发专项基金(BE2015612)

摘　　要：目的研究中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)信号通路在猪静脉桥早期再狭窄模型中的表达及其作用机制,从而探索NGAL信号通路在冠状动脉旁路移植术术后静脉桥血管早期再狭窄发生中的作用及相关机制。方法选择健康的普通长白猪18只,体重25~30 kg。对猪静脉桥再狭窄模型建立前、建立后7 d、14 d、30 d共4个时间点的静脉桥标本进行检测,并与未移植的大隐静脉进行对比,采用苏木素-伊红(HE)染色,Masson染色,免疫组织化学等方法,观察静脉桥血管内膜增生、平滑肌细胞迁移和血管重塑的情况,并对NGAL、基质金属蛋白酶(MMP)9、MMP2、组织金属蛋白酶抑制剂(TIMP)1等因子在不同桥血管中的表达变化情况进行检测。结果通过HE与Masson染色,随着建模时间的推移,桥血管胶原基质逐渐降解,肌纤维增厚并向内膜迁移,血管重塑,导致桥血管的狭窄。通过免疫组织化学结果可以看出,动物模型中NGAL、MMP9、MMP2因子在正常静脉桥血管中极少表达甚至不表达。建模后第14 d血管中膜层开始出现NGAL表达,第30 d中膜层NGAL表达达到高峰,并且内膜层开始出现表达。MMP9、MMP2在建模后第7 d开始出现表达,表达高峰出现在建模第14 d,30 d后表达趋于正常水平。正常血管壁TIMP1表达较少,建模后第14 d血管中的表达达到高峰。结论 NGAL、MMP9、MMP2、TIMP1等因子可能参与了桥血管早期再狭窄的形成,NGAL作为起始因子,导致MMP9、MMP2的表达增加,参与基质的降解和平滑肌细胞向内膜迁移。TIMP1等作为负性因子,对维持自身平衡可能起到重要的作用。Objective To investigate the expression of neutrophil gelatinase-associated lipocalin （NGAL） signaling pathways in the early stage of porcine vein graft restenosis, and to explore the possible role and mechanism in the early vein graft restenosis after coronary artery bypass surgery. Methods We selected 18 ordinary healthy pigs weighing 25-30 kg and collected samples of the vein graft of pigs at the preoperation and postoperative days 7, 14 and 30. Hematoxylin-eosin （liE） staining and Masson staining, immunohistochemical method were used to observe the neointimal hyperplasia, the migration of smooth muscle cells and and vascular remodeling of the vein bypass graft. The expression changes of NGAL, matrix metalloprotenase （MMP）9, MMP2 and tissue inhibitor of metalloproteinase （TIMP） 1 in different periods of the vein bypass graft was tested. Results By HE and Masson staining, with the passing of modeling time, degradation of collagen matrix in the vein graft, gradually thickening of muscle fibers and the migration to the inner membrance and vascular remodeling caused the vascular stenosis. By immunohistochemistry, NGAL, MMP9 and MMP2 of normal vein in the model were seldom expressed and even did not express. At 14 days after the rnndelingNGAL expression in the membrane layer of blood vessels began to appear, peaked at postoperative 30 days, and began to appear in the inner membrance. MMP9, MMP2 expression began to appear at postoperative 7 days, peaked at postoperative 14 days, and tended to decline at postoperative 30 days. TIMP1 expression was less in normal vascular walls and at the 14 days after the modeling, expression peaked in the vein graft. Conclusion NGAL, MMP9, MMP2 and TIMP1 may be involved in the formation of early vascular graft restenosis. NGAL as initiator, results in the expression of MMP9 and MMP2, and participates in the degradation of collagen matrix and the migration of smooth muscle cells in vein grafts. TIMP1 as a negative factor, may play an important role in maintaining thei

关 键 词：NGAL信号通路 静脉桥血管 平滑肌细胞 细胞外基质 血管再狭窄 

分 类 号：R-332[医药卫生] R654.2