PDTC干预对左向右分流大鼠模型肺动脉压力的影响

Effects of PDTC intervention on pulmonary artery pressure in left-to-right shunt rat models

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 explore the activity of NF-κB in pulmonary endothelial cells of left-to-right shunt model in rats and changes of pulmonary artery pressure after given a block agent（PDTC）.Methods 50 Wistar rats,aged 4 w,grouping 4 by computer randomly,shunt group（Tn） 15,blocked by PDTC after operation group（Ti） 15,sham operation control group（Co） 10,negative control group 10（Cn）.30 rats（Tn＋Ti） are set up left-to-right shunt type pulmonary hypertension model through the carotid artery-external jugular vein anastomosis,the total 15 rats（Ti group） are given PDTC by intraperitoneal injection before operation 1 h,dosage 120 mg·kg^-1·d^-1,after that,continue 2 w without the anastomosis,Co group rats have the identical operative procedure.After raising 12 w continuously,cardiac catheterization are used to survey right ventricle systolic pressure（RVSP）;and then dissociate pulmonary arterial endothelial cells,determine the binding activity of endothelial cells in every group and special gene recognition sequence by EMSA（Electrophoretic Mobility Shift Assay）.Results Tn group（activation of NF-κB） is evidently higher than Cn group（P〈0.01）,Ti group is lower than Cn group（P〈0.01） and Co group is not different statistically compared with Cn group.Tn group（lung vessel MT%） is obviously higher than Cn group（P〈0.01）.There is no statistical difference between Ti group and Tn group,and between Co group and Cn group.Conclusion Rat pulmonary vasoconstriction and structure remolding are related to augmented activity of NF-κB.PDTC can block NF-κB signaling pathway induced by high blood flow thus intervene the pulmonary vascular reconstruction.