猪肾动脉内膜去神经术对肾动脉内皮功能的影响及机制研究

摘要

Objective To study and evaluate the changes in endocrine function of renal arterial endothelial cells and possible mechanism on routinely temperature-controlled cardiac radiofrequency ablation catheter-based renal sympathic denervation in the acute phase.Methods 6 minipigs were performed bilateral renal artery angiography and radiofrequency ablation catheter-based unilateral renal sympathic denervation.Treated renal arteries served as operation group (n=6),and contralateral renal arteries untreated acted as sham-operation group (n=6).Pigs were examined for angiography again after the procedure and were euthanized immediately.Renal arteries were taken out and processed for histological,molecular biological analyzes to compare the changes of renal arterial structure and endothelial function in both groups.Results Compared to the sham-operation group,renal denervation caused renal arterial spasm,lacking immunostaining for von Willebrand Factor of endothelial cell,vacuolar degeneration of smooth muscle cells and adventitial axons,the decrease of gene expression (0.97±0.02 vs 0.61±0.08,0.98± 0.13 vs 0.35±0.02,all P＜0.01) and the down-regulation of phosphorylation level (0.62±0.23 vs 0.12±0.04,0.75±0.22 vs 0.29±0.17,all P＜0.01) of protein kinase B-endothelial-nitric oxide synthase signaling pathway,the increase of gene expression (0.52± 0.04 vs 0.82 ± 0.10,P＜0.01) and the up-regulation of protein expression (0.15±0.05 vs 0.34±0.08,P＜0.01) of endothelin 1,the increase of gene expression (0.55±0.03 vs 0.85±0.10,P＜0.01) and the up-regulation of protein expression (0.13 ±0.04 vs 0.27 ±0.06,P＜0.01) of endothelin A receptor.Conclusions In the swine model,renal sympathic denervation caused injury of renal arterial wall structure in an acute phase,which led to endocrine dysfunction of endothelial cells.The safety needed to be further assessed.%目的 使用常规温控心脏射频消融导管肾动脉去交感神经术,对肾动脉内皮细胞内分泌功能的急性期改变及可能的机制进行研究和评价.方法 6头小型猪均被行双侧肾动脉造影术和射频消融导管介导的单侧肾动脉去交感神经术.消融侧肾动脉为手术组(n=6),对侧未消融肾动脉为假手术组(n=6).术后猪均被再次造影后立即行安乐死.取肾动脉进行组织学染色、分子生物学分析以比较两组肾动脉结构和内皮细胞功能改变.结果 与假手术组相比,手术组急性期引起肾动脉痉挛,内皮细胞血管性血友病因子免疫染色缺失,中膜平滑肌细胞和外膜神经轴突空泡变性,蛋白激酶B-一氧化氮合酶信号通路基因表达减低(0.97±0.02比0.61±0.08,0.98±0.13比0.35±0.02,均P＜0.01)和磷酸化水平下调(0.62±0.23比0.12±0.04,0.75±0.22比0.29±0.17,均P＜0.01),内皮素1基因表达增加(0.52±0.04比0.82±0.10,P＜0.01)和蛋白表达上调(0.15±0.05比0.34±0.08,P＜0.01),内皮素A受体基因表达增加(0.55±0.03比0.85±0.10,P＜0.01)和蛋白表达上调(0.13 ±0.04比0.27±0.06,P＜0.01).结论 在猪模型中,肾动脉射频消融术在急性期造成肾动脉壁结构损伤,进而引起内皮细胞内分泌功能障碍,其安全性需进一步评估.