过表达eNOS的MSCs移植抑制肺动脉高压大鼠NF-κB表达

Implantation of mesenchymal stem cells over-expressing eNOS prevents expression of NF-κB in rats with pulmonary arterial hypertension

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,Control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.Adult 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 injected 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.