摘要
目的以左肺切除(PE)+野百合碱(MCT)建立大鼠肺动脉高压(PAH)新生内膜模型,探讨磷酸二酯酶1C(PDE1C)在该模型肺组织中的表达水平及作用。方法采用单纯PE、MCT、PE+MCT(P+M)3种方法建立大鼠PAH模型;检测模型大鼠平均肺动脉压力(mPAP)、中膜厚度百分比、右心肥厚指数(RV/LV+S)比值,观察新生内膜形成和非肌性小动脉肌化程度,比较3种PAH动物模型肺血管重构模式的差异;采用免疫组化检测PDE1C在3种动物模型肺组织中的表达水平。结果 P+M组右肺腺泡内血管出现新生内膜病变,且动物出现严重右心室肥大,肺动脉中膜增厚,平均mPAP和无肌性血管肌化程度较其他模型显著增加。大鼠PAH新生内膜模型PDE1C蛋白表达显著增加(P<0.05)。结论 P+M模型能更好地模拟人类严重PAH的病理改变,是研究梗阻性PAH的最佳动物模型。PDE1C在PAH动物模型肺动脉平滑肌细胞中显著上调,可能成为肺动脉高压治疗的新靶点。
Objective To establish a neointima model of pulmonary arterial hypertension （PAH） in rats by pneumonectomy（PE） and monoerotatine（MCT）,and to investigate the expression and function of phosphodiesterase 1C （PDE1C） protein in this PAH model.Methods Three approaches were used to establish PAH model in rats：left lung PE group（PE group）,MCT injection group,and MCT injection after PE group （P＋M group）.Mean pulmonary arterial pressure（mPAP）,percentage of media thickness（MT%） and the ratio of right ventricular hypertrophy index （RV/LV＋S） of model rats were recorded.Morphological parameters relevant to neointima formation and the muscularization of nonmuscle pulmonary arterioles were observed,and the difference of pulmonary vascular remodeling pattern of the three PAH models was analyzed.The expression of PDE1C was detected in each group by immunohistochemitry.Results The P＋M group showed serious lesions in the neointim and right ventricular,and serious right ventricular hypertrophy,and the increasing MT of pulmonary arterials could be seen in the animals.Compared with other groups,P＋M group had a significantly higher mPAP and muscularization of nonmuscle arterioles developed significantly.Expression of PDE1C protein increased significantly in the neointima PAH model（P〈0.05）.Conclusion P＋M model is a good model for simulation of severe PAH in human , which is the best animal model for a study on the obstructive PAH.Up-regulation of PDE1C in pulmonary artery smooth muscle cells of PAH animal model might offer a new target for therapy of PAH in human .
出处
《广西医学》
CAS
2013年第4期418-421,共4页
Guangxi Medical Journal
关键词
肺动脉高压
血管重构
新生内膜
磷酸二酯酶
动物模型
大鼠
Pulmonary hypertension
Vascular remodeling
Neointima
Phosphodiesterase
Animal model
Rat
