不同剂量野百合碱诱导SD幼鼠右室阻力负荷性心力衰竭模型的比较

目的采用不同剂量野百合碱(monocrota line,MCT)诱导SD幼鼠右心衰竭模型,探讨适合的右心衰竭模型制作方法。方法清洁级SD雄性幼鼠125只,随机分为G0、G1、G2、G3、G4组,每组各25只SD幼鼠。G1～G4组幼鼠分别一次性腹腔注射MCT 30、40、50、60 mg/kg,诱导制作右心衰竭动物模型;G0组为对照组,给予生理盐水腹腔注射。腹腔注射后每2周1次,采用彩色多普勒超声仪测SD幼鼠右心室横径、三尖瓣反流速度、肺动脉压、射血分数(EF值)、缩短分数(FS值),共检测6周,4次;随后处死SD幼鼠,取心脏、肺组织病理切片对比观察。结果 G0组SD幼鼠无死亡,G1、G2、G3组SD幼鼠的死亡率远远低于G4组。各组SD幼鼠右心室横径逐渐增大,G1～G4组较G0组更明显(P<0.01);G0组SD幼鼠各时期的三尖瓣反流速度、肺动脉压无明显改变,而G1～G4组逐渐增高(P<0.01)。G1组SD幼鼠肺动脉仅出现轻度新生内膜病变,心脏组织病理切片无明显改变;G2组SD幼鼠肺动脉可见较明显新生内膜病变,心脏组织病理切片可见明显炎性细胞浸润;G3、G4组SD幼鼠肺组织病理切片可见中小动脉中膜明显增厚和小动脉肌化,部分肺组织远端小动脉闭塞,肺泡内可见心衰细胞,右室心肌细胞肥大伴纤维组织增生。结论 50 mg/kg MCT可成功诱导建立肺动脉高压致右心衰竭模型,其病理变化可更好模拟重度肺动脉高压致右心衰竭,且实验动物有较高的生存率。

Evaluation dose of right ventricular failure model induced by different dose of MCT in young SD rats

Objective To establish right ventricular failure model by using different doses of MCT in young SD rats and to explore the optimal method for model establishment.Methods One hundred and twenty five SPF Sprague Dawley male rats were randomly divided into 5 groups(G0-G4)and each group had 25 rats.Different doses of monocrotaline of 30 mg/kg,40 mg/kg,50 mg/kg and 60 mg/kg were given to rats in Group 1 to 4 through intraperitoneal injection respectively in order to establish the model of right ventricular failure,and rats in Group 0(control group)were given physiological saline.Right ventricular transverse diameter(RVTD),tricuspid regurgitation velocity(TRV),pulmonary arterial pressure(PAH),ejection fraction(EF)and fractional shortening(FS)were measured by Color Doppler ultrasound once every other weeks after intraperitoneal injection for 8 weeks.Tissue sections of heart and lung tissues were made after the rats were put to death.Results The rats in G0 were all alive,mortality of rats in G1-G3 was far lower than that of rats in G4.The RVTD of each group increased gradually,especially in G1-G4(P < 0.01).TRV and PAH were equable over time in G0(P > 0.01),but increased day by day in G1-G4(P < 0.01).In rats of G1,only mild neointimal proliferation in pulmonary artery was observed,but there was no obvious change in tissue section of heart,In G2,obvious neointimal proliferation in pulmonary artery and evident infiltration of inflammatory cells in tissue section of heart were found,In G3 and G4,significant intima-media proliferation in small-to medium-sized pulmonary arteries and muscularization in small pulmonary arteries were observed,and even,some distal arteriole occluded.Meanwhile heart failure cells were found in pulmonary alveoli and hypertrophy accompanied with fibroplasia were found in myocardial cells of right ventricular.Conclusions By using 50 mg/kg of MCT,optimal right ventricular failure rat model can be established,because its pathological change is more similar to right ventricular failure in human being induced by severe pulmonary hypertension and survival rate in rats is high.