亚高原地区野百合碱诱导大鼠肺动脉高压模型的剂量研究

Dose Research of Monocrotaline Induced Pulmonary Arterial Hypertension in Rats at Moderate Altitude

目的探讨亚高原地区野百合碱(monocrotaline,MCT)诱导大鼠肺动脉高压模型的最佳剂量。方法将从平原地区购买85只♂SD大鼠随机分为对照组、MCT-20 mg·kg^(-1)组、MCT-30 mg·kg^(-1)组、MCT-40 mg·kg^(-1)组、MCT-50 mg·kg^(-1)组、MCT-60 mg·kg^(-1)组。除对照组外,所有大鼠于同日接受单次不同浓度MCT皮下注射,随后置于亚高原地区饲养,MCT注射第28天末采用右心导管术检测大鼠平均肺动脉压力,并计算大鼠右心室肥厚指数以评估右心肥厚程度,取大鼠肺组织行HE染色以评价肺血管重构情况,同时将大鼠的一般情况、生存率、体质量变化、脏器系数、血液学指标和模型成功率作为辅助评价指标。结果与对照组比较,单次皮下注射MCT-30,40,50,60 mg·kg^(-1)均可引起大鼠平均肺动脉压力增高、右心室肥厚和血管重构(P<0.05),模型符合肺动脉高压诊断标准。结论30 mg·kg^(-1)是亚高原地区MCT诱导大鼠肺动脉高压模型的最佳剂量。

OBJECTIVE To explore the optimal dose of monocrotaline(MCT)induced pulmonary arterial hypertension in rats at moderate altitude.METHODS Eighty-five male SD rats were randomly divided into control group,MCT-20 mg·kg^(-1) group,MCT-30 mg·kg^(-1) group,MCT-40 mg·kg^(-1) group,MCT-50 mg·kg^(-1) group and MCT-60 mg·kg^(-1) group.Except for the control group,all rats received a single subcutaneous injection of MCT,and then were raised in moderate altitude area.Right heart catheterization was used to determine the mean pulmonary artery pressure(mPAP)after 28 d.The right ventricular hypertrophy index was calculated as a parameter of right ventricular hypertrophy.Vascular remodeling was assessed by HE staining.In addition,the general condition,survival rate,body weight,organ coefficient,hematological indexes and success rate of the model in rats were used as auxiliary evaluation indexes.RESULTS Compared with the control group,single subcutaneous injection of MCT-30,40,50,60 mg·kg^(-1) could cause increased mPAP,right ventricular hypertrophy and vascular remodeling in rats(P<0.05).The model met the diagnostic criteria for pulmonary arterial hypertension.CONCLUSION MCT-30 mg·kg^(-1) is the optimal dose to induce pulmonary arterial hypertension in rats at moderate altitude.