高血流在大鼠肺动脉高压形成中的作用
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摘要
目的:本实验通过建立左肺切除、皮下注射野百合碱、左肺切除合并皮下注射野百合碱三种大鼠肺动脉高压模型,并设立对照组,以探讨细胞凋亡异常在大鼠肺动脉高压形成中的作用,并通过三组模型之间对比以明确高血流在促使细胞凋亡异常发生中的作用,从而探讨高血流在大鼠肺动脉高压形成中的作用
方法:将60只250-350克雄性wistar大鼠随机分成4组,分别行左肺切除术(PE组),皮下注射野百合碱(MCT组),左肺切除合并皮下注射野百合碱(PE+MCT组),并设立对照组(对照组),每组15例。检测平均肺动脉压力(mPAP)、右心指数RV/(LV+S)重量比值、肺小动脉中膜厚度百分比(WT% )、无肌性动脉肌化程度,并取肺组织行免疫组织化学法检测bcl-2和Survivin基因的表达情况。运用SPSS13.0统计软件进行数据分析。
结果:模型制作35天后,行右心导管检查显示:实验组大鼠与对照组相比,肺动脉压力不同程度升高,且PE+MCT组较MCT组和PE组升高明显;行纤维染色后观察肺组织结构:实验组大鼠肺组织血管内膜较对照组有不同程度的增厚,PE+MCT组较MCT组和PE组增厚明显,且肺动脉内壁新生内膜形成;行免疫组织化学检测Bcl-2和Survivin,PE组、MCT组、PE+MCT组肺组织血管外膜及血管周围细胞不同程度阳性表达,且PE+MCT组强于MCT组和PE组,结果有统计学意义。
结论:三种方法均有效建立了肺动脉高压大鼠模型,且PE+MCT组形成了重度肺动脉高压大鼠模型;在PE+MCT肺动脉高压大鼠模型的肺组织中,Bcl-2和Survivin表达增强,使肺组织细胞凋亡减少,血管壁细胞堆积,参与肺血管结构重塑。另外,PE组肺动脉高压大鼠模型的肺组织中,Bcl-2和Survivin亦有明显表达,高血流可作为独立因素诱发这一过程,是肺动脉高压形成的充分条件。
Objective--Impaired apoptosis of cells is associated with sever pulmonary artery hypertension which develop concentric-laminar intimal fibrosis and plexiform lesions. The aim of the present study was to observed the impaired apoptosis of cells in pneumonectomy (PE), monocrotaline (MCT), PE,+MCT pulmonary artery hypertension (PAH) animal model respectively and analyze the different between them to characterise the effects of increased pulmonary flow induced by left pneumonectomy in the PAH rat model .
Methods--Male wistar rat develop four group to develop to (1)PE PAH model, (2)MCT PAH model,(3)PE+MCT PAH model, and (4)control. We study the hemodynamics ,the microanatomy of lung of the model. In addition we assessed apoptosis-related markers in vascular and perivascular cells in lung samples from those models.
Results--The rats of PE, MCT and MCT+PE had a higher mean PAP than the rats of control; PE,MCT and MCT+PE all showed a comparably increased mean percentage wall thickness and abnormal extension of muscle into distal pulmonary arteries, These values were markedly increased compared with control rat (P<0.01); The antiapoptotic marker Bcl-2 and Survivin was expressed in the cells around pulmonary artery of PE,MCT and MCT+PE group and never expressed in control group.
Conclusions: PE+MCT PHT model is strongly associated with impaired cell apoptosis , these cell may be fibroblast. Increased pulmonary blood flow and monocrotaline-induced could result in impaired apoptosis of these cells respectively. High-flow may attribute to sever pulmonary hypertension as a independent factor rather than only a requirement.
方法:将60只250-350克雄性wistar大鼠随机分成4组,分别行左肺切除术(PE组),皮下注射野百合碱(MCT组),左肺切除合并皮下注射野百合碱(PE+MCT组),并设立对照组(对照组),每组15例。检测平均肺动脉压力(mPAP)、右心指数RV/(LV+S)重量比值、肺小动脉中膜厚度百分比(WT% )、无肌性动脉肌化程度,并取肺组织行免疫组织化学法检测bcl-2和Survivin基因的表达情况。运用SPSS13.0统计软件进行数据分析。
结果:模型制作35天后,行右心导管检查显示:实验组大鼠与对照组相比,肺动脉压力不同程度升高,且PE+MCT组较MCT组和PE组升高明显;行纤维染色后观察肺组织结构:实验组大鼠肺组织血管内膜较对照组有不同程度的增厚,PE+MCT组较MCT组和PE组增厚明显,且肺动脉内壁新生内膜形成;行免疫组织化学检测Bcl-2和Survivin,PE组、MCT组、PE+MCT组肺组织血管外膜及血管周围细胞不同程度阳性表达,且PE+MCT组强于MCT组和PE组,结果有统计学意义。
结论:三种方法均有效建立了肺动脉高压大鼠模型,且PE+MCT组形成了重度肺动脉高压大鼠模型;在PE+MCT肺动脉高压大鼠模型的肺组织中,Bcl-2和Survivin表达增强,使肺组织细胞凋亡减少,血管壁细胞堆积,参与肺血管结构重塑。另外,PE组肺动脉高压大鼠模型的肺组织中,Bcl-2和Survivin亦有明显表达,高血流可作为独立因素诱发这一过程,是肺动脉高压形成的充分条件。
Objective--Impaired apoptosis of cells is associated with sever pulmonary artery hypertension which develop concentric-laminar intimal fibrosis and plexiform lesions. The aim of the present study was to observed the impaired apoptosis of cells in pneumonectomy (PE), monocrotaline (MCT), PE,+MCT pulmonary artery hypertension (PAH) animal model respectively and analyze the different between them to characterise the effects of increased pulmonary flow induced by left pneumonectomy in the PAH rat model .
Methods--Male wistar rat develop four group to develop to (1)PE PAH model, (2)MCT PAH model,(3)PE+MCT PAH model, and (4)control. We study the hemodynamics ,the microanatomy of lung of the model. In addition we assessed apoptosis-related markers in vascular and perivascular cells in lung samples from those models.
Results--The rats of PE, MCT and MCT+PE had a higher mean PAP than the rats of control; PE,MCT and MCT+PE all showed a comparably increased mean percentage wall thickness and abnormal extension of muscle into distal pulmonary arteries, These values were markedly increased compared with control rat (P<0.01); The antiapoptotic marker Bcl-2 and Survivin was expressed in the cells around pulmonary artery of PE,MCT and MCT+PE group and never expressed in control group.
Conclusions: PE+MCT PHT model is strongly associated with impaired cell apoptosis , these cell may be fibroblast. Increased pulmonary blood flow and monocrotaline-induced could result in impaired apoptosis of these cells respectively. High-flow may attribute to sever pulmonary hypertension as a independent factor rather than only a requirement.
引文
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27.李荣,别毕华,张珍祥.慢性缺氧大鼠肺血管c-myc及bcl-2基因表达研究.中国组织化学与细胞化学杂志,1998,7:421-424.
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24.杨成,王胜发,王巨.凋亡机制在先天性心脏病肺动脉高压肺血管结构改建中的作用.中华胸心血管外科杂志,2001,17:355-357.
25. McMurtry MS, Archer SL, Altieri DC, et al. Gene therapy targeting surviving selectively induce pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. J Clin Invest, 2005;115: 1479-1491
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