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福辛普利与缬沙坦对肾动脉狭窄大鼠模型心脏纤维化和微循环的作用

Effects of fosinopril and valsartan on fibrosis and microcirculation function of heart in rat renal artery stenosis model

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【作者】 董豪坚; 叶景光; 罗德谋; 欧艳秋; 李光; 黄文晖; 周颖玲; 罗建方;

【Author】 DONG Hao-jian;YE Jing-guang;LUO De-mou;OU Yan-qiu;LI Guang;HUANG Wen-hui;ZHOU Ying-ling;LUO Jian-fang;Department of Cardiology,Guangdong Cardiovascular Institute,Guangdong Provincial People′s Hospital,Guangdong Academy of Medical Sciences;

【机构】 广东省心血管病研究所心内科广东省人民医院(广东省医学科学院);

【摘要】 目的以肾动脉狭窄大鼠模型[两肾一夹(two kidney one clip,2K1C)]为实验动物,对比福辛普利(fosinopril,Fos)和缬沙坦(valsartan,Val)干预后心脏组织纤维化以及冠状动脉微血管生成变化情况,比较两药对肾动脉狭窄患者心脏保护作用的异同。方法将20周龄的清洁级Wistar雄性大鼠(体质量260~290 g)20只分为4组,5只为空白组,15只成功建模2K1C:分为Fos组5只,Val组5只,模型组5只。Fos组和Val组分别给予Fos 15 mg·kg-1·d-1和Val 75 mg·kg-1·d-1,每天单次灌胃,其余两组大鼠喂养等量0.9%氯化钠溶液。干预4周后行心脏超声检查,并测量有创动脉、左心室压力,下腔静脉取血测量相关指标,解剖大鼠,取心脏组织行心脏纤维化病理检查、免疫组化测量冠状动脉微血管密度。结果药物干预4周后Fos组和Val组高血压与左心室肥厚均较模型组明显改善,差异有统计学意义(P<0.05);Fos组和Val组改善程度比较,差异无统计学意义(P>0.05)。Fos组和Val组血管内皮生长因子(vascular endothelial growth factor,VEGF)表达、CD31表达水平升高,Val组高于Fos组,并明显高于空白对照组,与模型组比较差异也有统计学意义(P<0.05)。结论 Fos和Val均可增加肾动脉狭窄大鼠心脏冠状动脉微血管密度,改善微循环,且后者效果更佳,两药有效减轻左心室肥厚,但未能逆转心脏纤维化。

【Abstract】 Objectives Basing on the mouse-model with unilateral renal artery stenosis(two kidney one clip,2K1C)set previously,fosinopril(Fos)and valsartan(Val)therapeutic effect on fibrosis and microcirculation function of heart was compared. Methods A total of 20 Wistar male mice in 20-week-old were divided into 4 groups with 5 rats each:sham group,control group(2K1C),Fos group(2K1C)and Val group(2K1C),the last two of which were given by gavage with Fos 15 mg·kg-1·d-1 and Val 75 mg·kg-1·d-1 separately. Echocardiography,invasive blood pressure,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 Comparing with sham and control group,left ventricular hypertrophy relieved apparently in both of Fos group and Val group to the same extent(P<0.05),while the difference between Fos group and Val group had no significant(P>0.05). Expressions of vascular endothelial growth factor(VEGF)and CD31 in both Fos group and Val group were significantly higher than those in sham group and control group(P<0.05),and further,expressions of VEGF and CD31 expression in Val group was the highest. Conclusions Fos and Val can both increase cardiac microvascular to improve the microcirculation status,and val works even better.Both of the medication can relieve left ventricular hypertrophy,while cannot reverse cardiac fibrosis.

【基金】 广东省医学科研基金项目(项目编号:A2017537)
  • 【文献出处】 岭南心血管病杂志 ,South China Journal of Cardiovascular Diseases , 编辑部邮箱 ,2019年03期
  • 【分类号】R692;R-332
  • 【被引频次】2
  • 【下载频次】89
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