Erythropoietin attenuates cardiac dysfunction by increasing myocardial angiogenesis and inhibiting interstitial fibrosis in diabetic rats.
Erythropoietin attenuates cardiac dysfunction by increasing myocardial angiogenesis and inhibiting interstitial fibrosis in diabetic rats.
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DOI：
10.1186/1475-2840-11-105
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发表时间：
2012-09-07
影响因子：
9.3
通讯作者：
Liu NF
中科院分区：
文献类型：
--
作者：
Lu J;Yao YY;Dai QM;Ma GS;Zhang SF;Cao L;Ren LQ;Liu NF
最近的研究表明，促红细胞生成素（EPO）在缺血模型中通过增加血管内皮生长因子（VEGF）的表达和减轻心肌纤维化在心脏中具有组织保护作用。本研究探讨了EPO对糖尿病大鼠心室重构和血管生长的影响。雄性SD大鼠随机分为3组：对照组、链脲佐菌素（STZ）诱导的糖尿病组和EPO治疗组，EPO剂量为1000 U/kg，每周皮下注射1次。12周后行超声心动图检查，采集外周血进行内皮祖细胞（EPCs）计数。取心肌组织，采用实时荧光定量PCR（RT-PCR）检测VEGF和EPOR受体（EPOR）mRNA的表达，Western blotting检测VEGF和EPOR蛋白的表达。采用免疫组化法检测心肌组织中VEGF、EPOR、转化生长因子β（TGF-β）和CD 31的水平。为了检测心肌肥大，进行I型胶原、III型胶原的免疫组织化学和苦味酸天狼星红染色，并测量心肌细胞横截面积。注射STZ 12周后，血糖显著升高，并保持持续升高。EPO治疗显著改善了心脏收缩力，减少了舒张功能障碍。注射EPO后，糖尿病大鼠外周血EPCs含量明显增加（27.85 ± 3.43%，P < 0.01）。EPO注射可显著增加糖尿病大鼠左室心肌组织毛细血管密度、EPOR和VEGF表达。EPO还能抑制间质胶原沉积和TGF-β表达。用EPO治疗通过增加VEGF和EPOR表达水平来保护糖尿病动物的心脏组织，从而改善血管再生和抑制心脏纤维化。
Recent studies revealed that erythropoietin (EPO) has tissue-protective effects in the heart by increasing vascular endothelial growth factor (VEGF) expression and attenuating myocardial fibrosis in ischemia models. In this study, we investigated the effect of EPO on ventricular remodeling and blood vessel growth in diabetic rats. Male SD rats were randomly divided into 3 groups: control rats, streptozotocin (STZ)-induced diabetic rats, and diabetic rats treated with 1000 U/kg EPO by subcutaneous injection once per week. Twelve weeks later, echocardiography was conducted, and blood samples were collected for counting of peripheral blood endothelial progenitor cells (EPCs). Myocardial tissues were collected, quantitative real-time PCR (RT-PCR) was used to detect the mRNA expression of VEGF and EPO-receptor (EPOR), and Western blotting was used to detect the protein expression of VEGF and EPOR. VEGF, EPOR, transforming growth factor beta (TGF-β), and CD31 levels in the myocardium were determined by immunohistochemistry. To detect cardiac hypertrophy, immunohistochemistry of collagen type I, collagen type III, and Picrosirius Red staining were performed, and cardiomyocyte cross-sectional area was measured. After 12 weeks STZ injection, blood glucose increased significantly and remained consistently elevated. EPO treatment significantly improved cardiac contractility and reduced diastolic dysfunction. Rats receiving the EPO injection showed a significant increase in circulating EPCs (27.85 ± 3.43%, P < 0.01) compared with diabetic untreated animals. EPO injection significantly increased capillary density as well as EPOR and VEGF expression in left ventricular myocardial tissue from diabetic rats. Moreover, EPO inhibited interstitial collagen deposition and reduced TGF-β expression. Treatment with EPO protects cardiac tissue in diabetic animals by increasing VEGF and EPOR expression levels, leading to improved revascularization and the inhibition of cardiac fibrosis.
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影响因子：
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作者：
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通讯作者：
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作者：
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