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目的建立大鼠单侧肾动脉狭窄(renal artery stenosis,RAS)模型(两肾一夹,2K1C),分析RAS对心脏结构功能、冠状动脉微循环情况的影响,探索RAS对肾外主要器官的影响及机制。方法 20周龄的清洁级Wistar雄性大鼠(体质量260~290 g)30只,按随机数字表法随机分为模型组(“U型”银夹钳夹左侧肾动脉)和假手术(Sham)组(单纯分离左侧肾动脉)。术后6周大鼠行心脏超声检查,并测量其有创动脉、左心室压力;大鼠下腔静脉取血测量相关指标,解剖大鼠行心脏病理检查,免疫组化测量心脏微血管密度。结果术后6周模型组收缩压[(144.00±3.16)mm Hg vs.(93.00±2.65)mm Hg,P<0.001;1 mm Hg=0.133 k Pa]及肾素浓度[(3.95±0.17)μmol/L/h vs.(1.94±0.05)μmol/L/h,P<0.001]较Sham组显著升高,差异有统计学意义(P>0.05)。心脏超声显示左心室肥厚增加,舒张功能减退。Masson染色示模型组心脏纤维化比例增加,Western-blot示血管内皮生长因子表达下降,免疫组化CD31标记冠状动脉微血管密度下降,与Sham比较,差异均有统计学意义(P<0.05)。结论 RAS大鼠模型血压明显升高、心肌肥厚及纤维化、冠状动脉微血管密度下降。RAS可能通过肾素-血管紧张素-醛固酮系统(RAAS)的过度激活及抑制血管内皮生长因子的表达来影响心血管系统功能。
Objective To establish a rat model of renal artery stenosis (RAS) (2 nephronsis and 2K1C) and analyze the effect of RAS on cardiac structure and coronary microcirculation and to explore the effect of RAS on the extrarenal renal organs And mechanism. Methods Thirty-week-old Wistar male Wistar rats (260-290 g body weight) were randomly divided into model group (left renal artery with “U” type silver clamp) and false Sham group (isolated left renal artery only). Six weeks after operation, the rats underwent echocardiography, and their invasive arteries and left ventricular pressure were measured. Relevant indexes were measured in inferior vena cava of rats. Cardiac pathological examination was performed in rats. The density of cardiac microvessels was measured by immunohistochemistry. Results Compared with model group, systolic blood pressure ((144.00 ± 3.16) mm Hg vs (93.00 ± 2.65) mm Hg, P <0.001, 1 mm Hg = 0.133 kPa and renin concentration were (3.95 ± 0.17) μmol / L / h vs. (1.94 ± 0.05) μmol / L / h, P <0.001] was significantly higher than Sham group (P> 0.05). Echocardiography showed increased left ventricular hypertrophy and decreased diastolic function. Masson staining showed that the proportion of cardiac fibrosis was increased, the expression of VEGF was decreased by Western-blot, and the density of CD31-labeled coronary artery was decreased in the model group compared with Sham group (P <0.05). Conclusion The blood pressure of RAS rat model is obviously increased, and the cardiac hypertrophy and fibrosis and the decrease of coronary microvascular density. RAS may affect cardiovascular system function through over-activation of renin-angiotensin-aldosterone system (RAAS) and inhibition of vascular endothelial growth factor expression.