内皮祖细胞与雌激素联合应用防止PCI术后再狭窄的研究

山东大学学报(医学版) ›› 2009, Vol. 47 ›› Issue (10): 39-44.

内皮祖细胞与雌激素联合应用防止PCI术后再狭窄的研究

徐付彪¹，李继福¹，户克庆¹，邵娜¹，刘春喜²，杨智²

1．山东大学齐鲁医院心内科； 2．教育部与卫生部心血管功能与重构重点实验室，济南 250012

收稿日期:2009-04-23 出版日期:2009-10-16 发布日期:2009-10-16
通讯作者: 李继福（1962- ），男，教授，主要从事冠心病介入治疗和动脉粥样硬化的研究。 Email:jifuli1028@yahoo.com.cn
作者简介:徐付彪（1981- ），男，硕士研究生，主要从事动脉粥样硬化的研究。E mail:fbxu2002@yahoo.cn
基金资助:
山东省科技厅资助课题(Y2006)。

Endothelial progenitor cells in combination with estrogen against 
restenosis after percutaneous coronary intervention

XU Fubiao¹,　LI Jifu¹, 　HU Keqing¹,　SHAO Na¹,　LIU Chunxi²,　YANG Zhi²

1． Department of Cardiology, Qilu Hospital of Shandong University; 2． Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of  Education and Ministry of Health, Jinan 250012, China

Received:2009-04-23 Online:2009-10-16 Published:2009-10-16

摘要/Abstract

摘要：

目的探讨内皮祖细胞（EPC）与雌激素联合应用防止PCI术后再狭窄的效果。方法雌性新西兰大白兔60只随机分为5组，每组12只。Ⅰ：假手术组；Ⅱ：对照组；Ⅲ：雌激素组；Ⅳ：EPC组；Ⅴ：雌激素+EPC组。卵巢切除术后，Ⅲ组和Ⅴ组给予雌激素替代治疗，其余动物皮下注射生理盐水，卵巢切除前及卵巢切除后3?d、2周分别采血，应用放免法检测血清雌激素水平。实验动物高脂饮食6周后应用氧化酶法检测血浆总胆固醇、甘油三酯水平；用直接法检测低密度脂蛋白胆固醇及高密度脂蛋白胆固醇。从兔外周血分离培养单个核细胞，制备EPC悬液以备细胞移植。建立兔腹主动脉损伤模型，Ⅰ组动物仅分离暴露出股动脉而不做球囊损伤，Ⅳ组和Ⅴ组动物损伤血管局部经导管给予EPC悬液2?mL输注，其余动物（除Ⅰ组外）给予生理盐水2?mL,4周后，伊文斯蓝染色检测损伤血管段内皮修复程度，免疫组化法检测细胞增殖程度，HE染色观察管腔丢失情况。结果与Ⅰ、Ⅱ、Ⅳ组相比，Ⅲ、Ⅴ组雌激素水平明显升高（P＜0.01）,总胆固醇、低密度脂蛋白胆固醇明显降低（P＜0.01），高密度脂蛋白胆固醇明显升高（P＜0.15），甘油三脂差异无统计学意义（P＞0.05）。Ⅴ组与Ⅲ、Ⅳ组相比，内皮修复程度、细胞增殖程度及管腔丢失程度差异有统计学意义，分别为［(90.2±5.1)% vs (85.1±4.1)%、(83.9±6.5)%，P＜0.05］，［(15.67±2.98)% vs (26.02±4.18)%、(24.87±3.54)%，P＜0.01］,［(17.61±2.69)% vs (38.43±4.35)%、(41.15±4.45)%，P＜0.01］。结论EPC与雌激素联合应用能加速内皮修复，减少血管腔丢失。

关键词: 兔, 内皮祖细胞, 雌激素, 再狭窄, 内皮化, 新生内膜增生

Abstract:

To investigate the effect endothelial progenitor cells (EPC) in combination with estrogen on restenosis after percutaneous coronary intervention． MethodsSixty New Zealand white rabbits were randomly divided into five groups: the sham operation group(groupⅠ), the control group(groupⅡ), the estrogen treated group(groupⅢ), the EPC treated group(groupⅣ), and the estrogen in combination with EPC group(groupⅤ)， with twelve rabbits in each group. Three days after ovariectomy, animals in groups Ⅲ and Ⅴ were treated with estrogen, and the others were given physiological saline. The level of estrogen was detected before ovariectomy, and on day 3 and 2 weeks after ovariectomy. Levels of blood lipids(including total cholesterol, triglyceride, high density lipoprotein choesterol and low density lipoprotein cholesterol) were also detected after hyperlipemia feeding for 6 weeks. Mononuclear cells were isolated from the establishing animal models of injured abdominal aorta, animals in the shamoperation group had the femoral artery exposed without injuries. At the same time, rabbits in groups Ⅳ and Ⅴwere subjected to suspension of EPC at 2ml through a catheter and the others（except Ⅰ group） were given physiological saline. Endothelium recovery, degree of cell proliferation and lumen loss were evaluated after 4 weeks. ResultsThe level of estrogen in groups Ⅲ and Ⅴwere obviously higher than that in groupsⅠ, Ⅱ and Ⅳ（P＜0.01）. The levels of blood lipids, including total cholesterol(P＜0.01）, low density lipoprotein cholesterol(P＜0.01）and high density lipoprotein choesterol(P＜0.05）were statistically different between groups Ⅲ,　Ⅴ and groupsⅠ, Ⅱ Ⅳ. There were also a statistical significance in the degree of endothelium recovery, cell proliferation and lumen loss between group Ⅴ and groups Ⅲ,　Ⅳ［(90.2±5.1)% vs (85.1±4.1)% and (83.9±6.5)%，P＜0.05］，　［(15.67±2.98)% vs (26.02±4.18)% and (24.87±3.54)%，P＜0.01］, and ［( 17.61±2.69)% vs (38.43±4.35)% and (41.15±4.45)%，P＜0.01］. ConclusionEPC in combination with estrogen after PCI can speed up the process of endothelial recovery and significantly reduces lumen loss.

Key words: Endothelial progenitor cells; Estrogen; Restenosis; Endothelialization; Neonitima proliferation; Rabbits

中图分类号:

R543

. 内皮祖细胞与雌激素联合应用防止PCI术后再狭窄的研究[J]. 山东大学学报(医学版), 2009, 47(10): 39-44.

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