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目的探讨核蛋白因子κB(NF-κB)在左向右分流大鼠模型肺动脉内皮细胞的活性及应用阻断剂(PDTC)干预后肺动脉压力的变化。方法 50只4周龄Wistar雄性大鼠随机分为4组:手术分流组(Tn组)15只,手术+PDTC阻断组(Ti组)15只,假手术对照组(Co组)10只,阴性对照组(Cn组)10只。将Tn组和Ti组30只大鼠通过颈总动脉-颈外静脉吻合术建立左向右分流型肺动脉高压模型,其中Ti组15只大鼠于术前1 h开始腹腔注射PDTC,剂量为120 mg.kg-1.d-1,持续2周,Co组大鼠除了不进行颈总动脉-颈外静脉吻合外,其余手术程序与实验组完全相同。连续饲养12周后,采用心导管术测量右心室收缩压(RVSP);分离大鼠肺动脉内皮细胞,通过凝胶迁移率实验(EMSA)测定各组内皮细胞NF-κB与特定基因识别序列相结合的活性。结果 Tn组NF-κB活性明显高于Cn组(P<0.01),Ti组NF-κB活性低于Cn组(P<0.01),而Co组与Cn组相比无统计学差异。Tn组大鼠肺血管MT%与Cn组相比明显升高(P<0.01);而Ti组与Cn组相比无统计学差异(P>0.05);Co组与Cn组相比较无统计学差异(P>0.05)。结论高肺血流所致的大鼠肺血管收缩和结构重建与NF-κB的活性增强有关,阻断剂PDTC可以通过阻断高血流所致的NF-κB信号通路从而干预肺血管重建。
Objective To investigate the activity of nuclear factor kappa B (NF-κB) in pulmonary artery endothelial cells of left-to-right shunt rat model and the changes of pulmonary artery pressure after intervention with PDTC. Methods Fifty male Wistar rats of 4 weeks old were randomly divided into 4 groups: 15 in Tn group, 15 in Ti + group and 10 in Co group, Negative control group (Cn group) 10. Thirty rats in Tn group and Ti group were given left-right shunt pulmonary hypertension by carotid artery-external jugular vein anastomosis. Among them, 15 rats in Ti group were given intraperitoneal injection of PDTC at a dose of 120 mg.kg-1.d-1 for 2 weeks. The rats in Co group were the same as those in experimental group except that they did not receive carotid artery-external jugular vein anastomosis. Right ventricular systolic pressure (RVSP) was measured by cardiac catheterization after continuous feeding for 12 weeks. Pulmonary artery endothelial cells were isolated and the NF-κB activity in endothelial cells of each group was determined by specific mobility shift assay (EMSA) Activity. Results The NF-κB activity in Tn group was significantly higher than that in Cn group (P <0.01). The activity of NF-κB in Ti group was lower than that in Cn group (P <0.01). There was no significant difference between Co group and Cn group. Compared with Cn group, the MT% of Tn group was significantly higher than that of Cn group (P <0.01), but there was no significant difference between Ti group and Cn group (P> 0.05). There was no statistical difference between Co group and Cn group Difference (P> 0.05). Conclusion Pulmonary vasoconstriction and structural remodeling induced by high pulmonary blood flow may be related to the increased activity of NF-κB. Blocking agent PDTC may interfere with pulmonary vascular remodeling by blocking the NF-κB signaling pathway induced by high blood flow.