肾动脉狭窄大鼠模型的心脏结构及微循环改变

Impact of renal artery stenosis on heart structure and coronary microcirculation in mice model

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。

Objectives A mouse-model of unilateral renal artery stenosis（RAS）（two kidney one clip, 2K1C） was set to analysis the influences of RAS on cardiac structure and function, and coronary microcirculation. Influences of RAS to the extra- kidney- organism, as well as the detection of its mechanism were also analyzed. Methods A total of 30 Wistar male mice in 20-weeks-old were divided into two groups randomly, one of which was 2K1 C group（left renal artery was clipped with a U-shaped silver clip）, with the other as sham group（separate the left renal artery only）.Echocardiography was performed in each group at 6 weeks after the operation, and the examinations of invasive blood pressure,left ventricular pressure and serum markers from postcava were added to the analysis. Test of cardiac pathology and test of micro-vessel in heart by immuohistochemical test were also held on the experimental mice. Results After6 weeks, the systolic blood pressure and the serum renin concentration in 2K1 C group were much higher compared to those of the sham group [（144.00 ±3.16） mm Hg vs.（93.00 ±2.65） mm Hg, P〈0.001;1 mm Hg =0.133 k Pa;（3.95 ±0.17）μmol / L / h vs.（1.94±0.05） μmol / L / h, P〈0.001 ]. Compared with the sham group, left ventricular hypertrophy was more severe as well as the deficiency of diastolic function in 2K1 C group. There was a more severity in cardiac tissue in Masson dyeing, decreasing in expression of vascular endothelial growth factor（VEGF） in Western Blot,decreasing in dense of coronary micro-vessel in CD31-marked-immunohistochemical test in 2K1 C group compared with those in sham group, which had statistical difference. Conclusions In 2K1 C group, blood pressure is higher,myocardial hypertrophy and fibrous are severity, density of coronary micro-vessel decreases. RAS may influence the function of cardiovascular system by overstimulating the renin-angiotensin aldosterone system（RAAS） and inhibiting the expression of VEGF.