脱氢野百合碱诱导犬肺动脉高压模型的建立

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。

Establishment of a canine model of pulmonary hypertension with dehydromonocrotaline

Objective Pulmonary 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 dimefhylformamide 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-injeetion 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 dehydromonocrotaline-induced pulmonary hypertension model in dog was established successfully, which is characterized by neointimal proliferation and medial hypertrophy.