脱氢野百合碱诱导犬肺动脉高压模型的建立  

Establishment of a canine model of pulmonary hypertension with dehydromonocrotaline

作　　者：赵永红[1] 苏肇伉[2,1] 张海波[2,1] 陈会文[2,1] 蒋祖明[2,1] 邹文艳[2,1] 

机构地区：[1]上海儿童医学中心心胸外科 [2]上海第二医科大学附属新华医院,200127

出　　处：《中华胸心血管外科杂志》2005年第6期346-348,共3页Chinese Journal of Thoracic and Cardiovascular Surgery

基　　金：小课题受国家自然科学基金资助(30371407)

摘　　要：目的用药物法建立犬肺动脉高压模型。方法野百合碱经脱氢处理成脱氢野百合碱 (dehydromonocrotaline,DMCT),经心导管注射入犬右心房,于注射药物后4周、8周测定肺动脉压力等血液动力学参数,并行肺组织病理检查,评估周围肺肌性动脉肌化情况、肌性肺动脉中膜肥厚程度。结果 DMCT(3 mg／kg)组8只犬存活2只,DMCT(2 mg／kg)组8只犬与对照组犬均存活。DMCT组4周后平均肺动脉压(mMPAP)(20．7±3．1)mm Hg(1 mm Hg=0．133 kPa),8周后mPAP(30．2±2．6)mm Hg,肺动脉收缩压(sPAP)和肺动脉楔压(PCWP)亦升高,与给药前相比,差异有统计学意义(P<0．01)。DMCT组8周后 mPAP、sPAP与PCWP亦明显高于溶剂对照组,差异有统计学意义,P<0．01。8周后DMCT组直径为15- 50μm的肺肌性动脉肌化数(54．3±6．6)％,直径为100-200μm的肺肌性动脉的中膜厚度百分比(27．3± 5．7)％,均高于溶剂对照组,差异有统计学意义(P<0．01),右心肥大指数增加(P<0．05)。光学显微镜下观察到DMCT组肺泡区肺肌性动脉中膜肥厚,新生内膜形成,管腔变小。结论 DMCT可成功诱导犬肺动脉高压模型,模拟人类终末期肺高压的病理特点。Objective Puhnonary hypertension （PH） is a poorly understood disease process for which no adequate therapy exists. The aim of this study was to establish a relevant animal models, evaluate the hemodynamic and pathologic alterations that developed in dogs after the direct administration of dehydromonocrotaline （DMCT）. Methods Twenty four mongrel dogs were randomized into 3 groups. An injection of dimethylformamide of 0.1 ml/kg （ group 1, n = 8）, dehydromonocrotaline of 2 mg/kg （group 2, n = 8）, or 3 mg/kg （group 3, n = 8） was performed via the right atrium. Morphometric analysis was performed to assess the degree of pulmonary vascular remodeling. Results 6 dogs in group 3 died of acute pulmonary edema. The mean pulmonary arterial pressure, systolic pulmonary arterial pressure and pulmonary capilliary wedge pressure in group 2 increased significantly at 4 weeks after injection, and increased further at 8 weeks after injection compared with pre-injection and group 1. Pathologic analysis revealed the percent of pulmonary arterial muscularity and medial hypertrophy were significantly increased, furthermore, neointimal proliferation was observed in a large proportion of the analyzed pulmonary arteries in group 2 but never seen in the control group. Conclusion A new dehydromunocrotaline-induced pulmonary hypertension model in dog was established successfully, which is characterized by neointimal proliferation and medial hypertrophy.

关 键 词：野百合碱 高血压 肺性 疾病模型 动物 肺动脉高压模型 肌性动脉 血液动力学参数 氢 组织病理检查 平均肺动脉压 肺动脉收缩压 

分 类 号：R-332[医药卫生]