中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (37): 6863-6866.doi: 10.3969/j.issn.2095-4344.2012.37.005

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

内膜新生性肺血管重构肺动脉高压大鼠模型的建立及评价

梁富球1,林 群2,林财珠2,雷立华3,杨 庆2,林献忠2,蔡宏达2   

  1. 1 福建医科大学,福建省福州市 350004
    2福建医科大学附属第一医院麻醉科,福建省福州市 350005
    3 福建医科大学省立临床医学院麻醉科,福建省福州市 350001
  • 收稿日期:2012-01-08 修回日期:2012-02-04 出版日期:2012-09-09 发布日期:2012-09-09
  • 通讯作者: 林群,副主任医师,副教授,硕士生导师,福建医科大学附属第一医院麻醉科,福建省福州市 350005 linqun007@163.com
  • 作者简介:梁富球★,女,1987 年生,湖南省益阳市人,汉族,福建医科大学在读硕士,主要从事肺动脉高压基础与临床方面的研究。 409273133@qq.com

Establishment of a neointimal model of pulmonary hypertension induced by monocrotaline injury plus pneumonectomy in rats

Liang Fu-qiu1, Lin Qun2, Lin Cai-zhu2, Lei Li-hua3, Yang Qing2, Lin Xian-zhong2, Cai Hong-da2   

  1. 1Fujian Medical University, Fuzhou 350004, Fujian Province, China
    2Department of Anesthesiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
    3Department of Anesthesiology, Teaching Hospital of Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350014, Fujian Province, China
  • Received:2012-01-08 Revised:2012-02-04 Online:2012-09-09 Published:2012-09-09
  • Contact: Lin Qun, Associate chief physician, Associate professor, Master’s supervisor, Department of Anesthesiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China linqun007@163.com
  • About author:Liang Fu-qiu★, Studying for master’s degree, Physician, Fujian Medical University, Fuzhou 350004, Fujian Province, China 409273133@qq.com

摘要:

背景:目前尚缺乏简单易行、实用、操作性强的血管内膜新生性肺血管重构肺动脉高压动物模型。
目的:建立内膜新生性肺血管重构大鼠肺动脉高压模型。
方法:40只雄性SD大鼠随机分为2组:M+P组(n=26)大鼠行左肺切除,2周后皮下注射野百合碱60 mg/kg;对照组(n=14)大鼠仅行假手术处理。于术后5周检测肺动脉压、右心室/(左心室+室间隔)质量的比值,同时观察右肺动脉病理形态学改变。以光镜下每1 mm2面积内Ⅷ因子标记阳性的直径小于100 μm的肺血管数评价肺内微血管密度。
结果与结论:M+P组大鼠存活率85%(22/26),对照组存活率为100%(14/14)。与对照组相比,M+P组大鼠肺动脉压力和右心室/(左心室+室间隔)质量的比值明显增高(P < 0.01);与对照组相比,M+P组大鼠肺内直径为50-100 μm和100-150 μm的肌型小动脉中膜相对厚度均显著增加(P < 0.01),肺内微血管密度显著减少(P < 0.01)。光镜显示M+P组大鼠注射野百合碱后5周肌型肺小动脉中膜明显增厚,肺腺泡内小动脉明显肌化、内膜增厚。对照组大鼠肺小动脉未见血管结构重建。实验成功建立了内膜新生性肺血管重构大鼠肺动脉高压模型,操作相时简便,动物死亡率较低。

关键词: 野百合碱, 肺切除术, 肺动脉, 大鼠, 肺动脉高压, 血管构建, 动物模型, 组织构建

Abstract:

BACKGROUND: There is currently a lack of simple, practical, workable neointimal models of pulmonary hypertension in rats.
OBJECTIVE: To establish a neointimal model of pulmonary hypertension by monocrtaline injury plus pneumonectomy in rats.
METHODS: Forty male SD rats were randomly divided into two groups: monocrtaline+pneumonectomy group (experimental group) was subjected to left pneumonectomy followed by monocrotaline injected 2 weeks later (n=26); Control group only underwent sham operation (n=14). Pulmonary artery pressure, ventricular weight, and pulmonary artery morphology were evaluated at 5 weeks after operation in each group. Factor VIII-positive capillaries that were less than 100 μm in diameter were counted under microscopy for 10 randomly selected fields per specimen. The capillary density was determined as the average number of factor VIII-positive capillaries per 1 mm2.
RESULTS AND CONCLUSION: Four weeks after operation, 85% rats survived (22/26) in the experimental group, and 100% in the control group (14/14). The experimental group had significantly higher mean pulmonary artery pressures and ratio of right ventricular and left ventricular plus septal weights, as well as percent wall thickness of muscular pulmonary arteries ranging from 50 to 100 μm diameter and from 100 to 150 μm diameter were significantly increased as compared with the control group (P < 0.01). Pulmonary capillary density was less in the experimental group than in the control group (P < 0.01). Historic examination showed significant medial hypertrophy of muscularized pulmonary arteries and muscularization of intra-acinar pulmonary arteries and intimal thickening developed in right lung intracinar pulmonary arteries in the experimental group. However, there was no evidence of pulmonary vascular remodeling in the control group. Hemodynamic pulmonary hypertension and neointimal lesions could be quickly induced at 5 weeks after pneumonectomy plus monocrotaline injury. This method was easily performed and mortality of rats was relatively low.

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