目的探讨高血压对新生内膜形成的影响及部分可能机制。方法按双肾双夹法复制易卒中型肾血管性大鼠高血压模型(stroke-prone renovascular hypertensive rats,RHRSP),选取收缩压稳定在180 mm Hg以上、无自发性卒中表现的RHRSP,行左侧颈总动脉内膜剥除术。计算颈总动脉内膜、中膜面积和内膜/中膜面积比率。以抗CD31抗体标记内皮细胞检测再内皮化,以抗α-SMA抗体标记血管平滑肌细胞(vascular smoothmuscle cells,VSMCs),以流式细胞仪检测CXCR4+细胞占总单核细胞的百分比。结果对照正常血压组,高血压组的血压显著增高(203.36±17.31 mm Hg;95.5±10.01 mm Hg,P〈0.05,n=20),新生内膜面积增加(2.18±0.11 mm2;1.55±0.14 mm2,P=0.013,n=4),循环中CXCR4+细胞百分比增高(损伤前:30.11%±1.27%;20.91%±2.06%,P=0.019;损伤后7 d:45.64%±3.30%;28.28%±2.56%,P=0.003,n=3~5)。高血压不影响再内皮化,新生内膜的主要成分仍为VSMCs。结论高血压增加血管损伤之前和之后早期循环中的CXCR4+细胞,可能与其促进新生内膜形成有关。
Objective To investigate the influence of hypertension on carotid neointimal formation and the underlying mechanisms.Methods In this study,stroke-prone renovascular hypertensive rats(RHRSP) were used,and balloon injury was induced in the left carotid artery.Morphological analysis was performed to assess neointimal formation 2 weeks after carotid injury.Re-endothelialization and vascular smooth muscle cells(VSMCs) were detected using CD31 and anti-α-SMA antibodies,respectively.Circulating CXCR4+ cells were determined by using Fluorescence-activated cell sorting analysis.Results The systolic blood pressure was significantly and persistently increased in RHRSP(203.36 ± 17.31 mm Hg vs 95.5 ± 10.01 mm Hg,P 0.05,n = 20).Neointimal formation was exaggerated in hypertension(2.18 ± 0.11 mm2 vs 1.55 ± 0.14 mm2,P = 0.013,n = 4),and circulating CXCR4+ cell percentage was significantly in creased before and 7 days after carotid balloon injury(before injury: 30.11% ± 1.27% vs 20.91% ± 2.06%,P = 0.019;7 days post injury: 45.64% ± 3.30% vs 28.28% ± 2.56%,P = 0.003,n = 3 ~ 5).VSMCs were the main components of neointima in hypertension,while re-endothelialization remained identical in both normotension and hypertension.Conclusions This study domenstrates that hypertension enhances neointimal formation and increases circulating CXCR4+ cells before and early after carotid endothelial denudation,which may contribute to hypertension-induced endothelialization