不同剂量野百合碱诱导大鼠肺动脉高压模型的实验研究(英文)

Experimental Research of Pulmonary Arterial Hypertension Model Induced by Different Dose of MCT in SD Rats

目的:肺动脉高压患者的预后非常差并且目前对肺动脉高压的治疗缺乏有效的方法。因此,对肺动脉高压的研究十分迫切,而建立稳定、操作简便、稳定的肺动脉高压模型是研究肺动脉高压的基础。本实验的目的就是采用不同剂量野百合碱(monocro-taline,MCT)诱导建立SD大鼠肺动脉高压模型,探讨肺动脉高压模型的制作方法及其稳定性。方法:清洁级SD雄性大鼠75只,随机分为C组、M1、M2、M3和M4组,每组各15只。其中M1～M4组大鼠分别一次性腹腔注射MCT 30、40、50和60 mg/kg,诱导制作肺动脉高压动物模型;C组为对照组,给予相同剂量溶剂腹腔注射。腹腔注射4周后比较各组大鼠的生存率、检测平均肺动脉压力(mPAP),肺动脉收缩压(PASP),右心肥大指数(RVHI),并取肺组织行苏木素-伊红染色,观察肺的病理改变,采用肺小动脉形态计量学指标综合判断肺动脉高压模型的稳定性。结果:C组无死亡,M1～M4组大鼠的生存率分别为87%,87%,67%,40%。M1～M4各组SD大鼠平均肺动脉压、肺动脉收缩压、右心肥大指数依次增大(P<0.05),肺小动脉形态计量学指标检测显示肺血管中膜厚度百分比依次增大(P<0.05),而M3与M4组各测量结果无明显差异。结论:腹腔注射50 mg/kg、60 mg/kg剂量野百合碱均可引起大鼠肺动脉压力升高和肺血管重构,均可诱导稳定的肺动脉高压模型,而50 mg/kg剂量有更高的生存率。所以50mg/kg剂量野百合碱腹腔注射是成功诱导大鼠肺动脉高压模型的合适剂量。

Objective：The prognosis of patients with pulmonary arterial hypertension（PAH） is poor,and at present there is no effective treatment for PAH.Therefore,the study for PAH is very urgent,and to build stable,user-friendly controlled and applicative pulmonary arterial hypertension animal model is the basis for researching pulmonary arterial hypertension.The objective of our experiment is to establish PAH model by using different doses of monocrotaline（MCT） in SD rats and to explore the optimal method for model establishment.Methods： Seventy-five SPF Sprague-Dawley male rats were randomly divided into 5 groups,and there was 15 rats in each group.Different doses of monocrotaline of 30,40,50 and 60 mg/kg were given to rats in Group M1 to M4 through intraperitoneal injection respectively in order to establish the model of pulmonary arterial hypertension;and rats in Group C（control group） were given the same solvent.The survival rate,mean pulmonary arterial pressure（mPAP）,pulmonary arterial systolic pressure（PASP）,right ventricle hypertrophy index（RVHI）,the microstructural alteration of small pulmonary vessel were measured and tissue sections of lung were made after intraperitoneal injection for 4 weeks.Results： The rats in group C were all alive.The survival rate of rats in M1～M4 were 87%,87%,67% and 40%,respectively.The mean pulmonary arterial pressure,pulmonary arterial systolic pressure and right ventricle hypertrophy index in M1～M4 increased gradually（P0.05）,the morphometry indices of small pulmonary arteries reveal relative medial thickness increased gradually（P0.05）,but there is no significant difference in M3 and M4.Conclusion： Dose of MCT of 50 mg/kg and 60mg/kg will cause to rise pulmonary arterial pressure and remodel vascular of rats,both of which can induce the stable pulmonary arterial pressure model,while dose of 50mg/kg has higher survival rate.So,intraperitioneal injection of monocrotaline with dose of 50 mg/kg is the appropriate dose to induce rats pulmonary arterial pressure model.