基础研究(Basic Research)

辛伐他汀对深静脉血栓形成中静脉壁重塑影响的实验研究

Published at: 2015年第24卷第12期

冯亚平 1 , 张福先 1 , 牛鹿原 1 , 张明逸 1
1 首都医科大学附属北京世纪坛医院 血管外科,北京 100038
通讯作者 福先 张 Email: fuxian@263.net
DOI: 10.3978/j.issn.1005-6947.10.3978/j.issn.1005-6947.2015.12.012
基金:
北京医药产品和技术重大项目培育研究资助项目 Z101107050210022

摘要

目的:探讨辛伐他汀对深静脉血栓形成(DVT)过程中静脉壁重塑的影响。 方法:将48 只新西兰兔制作DVT 模型48 h 后随机均分为4 组,分别给予生理盐水(对照组)、抗凝剂(抗 凝组)、辛伐他汀(他汀组)、抗凝剂+ 辛伐他汀(联合组)每天1 次干预,在干预过程中的不同时 间点检测各组动物病变静脉管壁病理变化以及胶原纤维与α- 平滑肌肌动蛋白(α-SMA)的表达。 结果: DVT 模型成功率为100%;病理学观察显示,随时间进展,各组动物静脉管壁均逐步出现明显 的局部炎症反应、中膜增生、内膜下纤维组织增生,但他汀组与联合组的病变程度明显轻于对照组与 抗凝组;Masson 染色结果显示,各组管壁胶原含量在不同时间点均依次为对照组> 抗凝组> 他汀组> 联合组(部分P<0.05);免疫组化结果显示,与对照组比较,他汀组与联合组管壁α-SMA 的表达量 减少,且随时间延长,联合组表现更为明显(部分P<0.05),但抗凝组在各时间点α-SMA 表达量均 无明显降低(均P>0.05)。 结论:辛伐他汀能减少血管壁炎症、血管平滑肌增生及胶原纤维沉积,从而有利于抑制DVT 过程中静 脉壁重塑,且与抗凝药物合用有增效作用。


Effects of simvastatin on venous wall remodeling following deep venous thrombosis: an experimental study

Abstract

Objective: To investigate the effect of simvastatin on venous wall remodeling during deep vein thrombosis (DVT). Methods: Forty-eight hours after DVT model establishment, 48 New Zealand white rabbits were equally randomized into four groups, and then once daily were administered normal saline (control group), anticoagulant drug (anticoagulation group), simvastatin (statin group) or simvastatin plus anticoagulant drug (combination group), respectively. At different time points during intervention, the pathological changes, deposition of collagen fibers and expression of α-smooth muscle actin (α-SMA) in the wall of the diseased vein from each group of animals were examined. Results: The success rate for DVT model establishment was 100%. Pathological examination found that, as time progressed, the affected venous walls in each group gradually exhibited evident local inflammation, medial thickness, and subintimal proliferation of fibrous tissue, but the degrees of these changes in statin group and combination group were markedly milder than those in control group and anticoagulation group. Results of Masson staining showed that the collagen content of the venous wall at each time point presented in a decreasing order as follows: control group>anticoagulation group>statin group>combination group (partial P<0.05). Results of immunohistochemical staining demonstrated that compared with control group, the α-SMA expression level of venous wall in statin group or combination group was decreased which was more evident in combination group over time (partial P<0.05), but the α-SMA expression level of venous wall showed no significant decrease in anticoagulation group at any time point (all P>0.05). Conclusion: Simvastatin can reduce inflammation, vascular smooth muscle proliferation and deposition of collagen fibers, which may inhibit the process of vascular remodeling of DVT, and these effects can be enhanced by combination with anticoagulants.


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引用

引用本文: 亚平 冯, 福先 张, 鹿原 牛, 明逸 张. 辛伐他汀对深静脉血栓形成中静脉壁重塑影响的实验研究[J]. 中国普通外科杂志, 2015, 24(12): 1696-1702.
Cite this article as: FENG Yaping, ZHANG Fuxian, NIU Luyuan, ZHANG Mingyi . Effects of simvastatin on venous wall remodeling following deep venous thrombosis: an experimental study[J]. Chin J Gen Surg, 2015, 24(12): 1696-1702.