Expression of tissue factor and forkhead box transcription factor O-1 in a rat model for chronic thromboembolic pulmonary hypertension

Expression of tissue factor and forkhead box transcription factor O-1 in a rat model for chronic thromboembolic pulmonary hypertension
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组织因子和叉头盒转录因子O-1在慢性血栓栓塞性肺动脉高压大鼠模型中的表达

DOI:
10.1007/s11239-016-1413-9
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发表时间:
2016-11-01
影响因子:
4
通讯作者:
Wu, Shuang
Wu, Shuang
中科院分区:
医学4区
文献类型:
--
作者:
Deng, Chaosheng;Wu, Dawen;Wu, Shuang

文献摘要

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组织因子(TF)和叉头盒转录因子O-1(FoxO1)在慢性血栓栓塞性肺动脉高压(CTEPH)动物模型中的表达很少见报道。目的:探讨转铁蛋白和FoxO1在大鼠慢性胰腺炎发病机制中的作用及其相互作用。将自体血栓经右颈静脉反复注入大鼠肺动脉,建立大鼠CTEPH模型。检测血流动力学参数、组织病理学、组织因子和FoxO1的表达水平。实验组平均肺动脉压(MPAP)、肺血管阻力及管壁面积/总面积(WA/TA)均较假手术组显著升高(P<0.05)。与假手术组相比,1周、2周和4周组的心输出量显著降低(P&lt;P&lt;P<0.05)。与假手术组相比,实验组Tf基因表达水平显著升高(P&lt;0.05)。实验组Foxo1基因和蛋白表达水平低于假手术组(P&lt;P&lt;0.05)。MPAP与WA/TA比值呈正相关(r=0.45,P=0.01)。TFmRNA表达与Wa/TA比值呈正相关(r=0.0.374,P=0.0.035),与mPAP呈正相关(r=0.48,P=0.005)。Foxo1mRNA表达与Wa/TA比值呈负相关趋势(r=0.−0.297,P=0.099),与mPAP呈负相关趋势(r=−0.34,P=0.057)。TFm RNA表达与FoxO1m RNA表达呈负相关(r=0.6 2,P<0.001)。将自体血块注入大鼠肺动脉可成功建立大鼠CTEPH模型。Tf和FoxO1可能在CTEPH的血管重塑中起关键作用。
Few reports have examined tissue factor (TF) and forkhead box transcription factor O-1 (FoxO1) expression in chronic thromboembolic pulmonary hypertension (CTEPH) animal models. To investigate the role of TF and FoxO1 and their interactions during CTEPH pathogenesis in a rat model. Autologous blood clots were repeatedly injected into the pulmonary arteries through right jugular vein to induce a rat model of CTEPH. Hemodynamic parameters, histopathology, and TF and FoxO1expression levels were detected. The mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance and vessel wall area/total area (WA/TA) ratio in the experiment group increased significantly than sham group (P< 0.05). The cardiac output in the 1-, 2-, and 4-week groups decreased significantly (P< 0.05) when compared to sham group. TF mRNA expression levels in the experiment group increased significantly than sham group (P< 0.05). FoxO1 mRNA and protein expression levels were lower in the experiment group than sham group (P< 0.05). The mPAP had a positive correlation with WA/TA ratio (r= 0.45,P= 0.01). TF mRNA expression had a positive correlation with WA/TA ratio (r= 0.374,P= 0.035) and a positive correlation with mPAP (r= 0.48,P= 0.005). FoxO1 mRNA expression had a negative correlation trend with the WA/TA ratio (r= −0.297,P= 0.099) and a negative correlation trend with mPAP (r= −0.34,P= 0.057). TF mRNA expression had a negative correlation with FoxO1 mRNA expression (r= −0.62,P< 0.001). A rat model of CTEPH can be successfully established by the injection of autologous blood clots into the pulmonary artery. TF and FoxO1 may play a key role in vascular remodeling during CTEPH pathogenesis.