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过表达eNOS的MSCs移植抑制肺动脉高压大鼠NF-κB表达

         

摘要

目的:研究过表达 eNOS的骨髓间充质干细胞(MSCs)移植对肺动脉高压(PAH)大鼠的 NF-κB影响。方法构建过表达eNOS基因骨髓间充质干细胞;成年雄性Sprague Dawley大鼠,建立分流性PAH模型36只,每组12只,Shunt组;MSCs组;MSCs+eNOS 组,正常大鼠为Control 组。由中心静脉注入细胞,2周后进行测定血流动力学指标及肺组织病理变化,westernblot及荧光定量PCR测定肺组织表达NF-κB的变化。结果 MSCs移植能降低右心室收缩压,减轻肺病理改变,MSCs+eNOS组下降更明显。NF-κB的 mRNA和蛋白表达在 Shunt组表达最强,Con-trol 组表达较弱,MSCs组、MSCs+eNOS组较Shunt组明显降低,且MSCs+eNOS组更显著。结论 MSCs和eNOS抑制高血流量PAH大鼠的 NF-κB表达对高血流量的发挥治疗作用。%Objective To observe effects of mesenchymal stem cells (MSCs)over-expressing eNOS on NF-κB in rats with pulmonary artery hypertension (PAH).Methods MSCs were transfected by lentivirus expressing eNOS gene.A-dult male Sprague Dawley rats were made as shunted PAH models,then were randomly divided into three groups:group shunt,group MSCs and goup MSCs+eNOS(n=12,respectively).The control group was matched normal rat.MSCs were inj ected through central vein.Two weeks later,hemodynamic index and lung biopsy were determined.Fluorescence quantitative PCR (FQ-PCR)and Westernblot were used to determine the level of NF-κB.Results MSCs can reduce right ventricular systolic pressure and attenuated lung’s lesions.And it was more obviously in group MSCs+eNOS. The level of mRNA and protein of NF-κB was highest in group shunt,lower in group MSCs but lowest in group MSCs+eNOS.Conclusion MSCs and eNOS act on rats with high flow PAH by preventing the expression of NF-κB.

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