促红细胞生成素对慢性心肌梗死大鼠的心肌HIF及VEGF表达研究

The Effects of Erythropoietin on the Expression of HIF and VEGF in Myocardium of Rats with Chronic Myocardial Infarction

目的探讨促红细胞生成素对慢性心肌梗死(心梗)大鼠微血管再生的调节作用。方法雄性SD大鼠30只随机分为假手术对照组、心肌梗死对照组和EPO治疗组。心肌梗死对照组及EPO治疗组运用结扎左冠状动脉前降支建立心梗模型。EPO治疗组术后每天腹腔注射EPO(1000IU.kg-1),其余两组注射等量生理盐水。术后30d,分别测定各组大鼠心功能,同时用免疫组化方法测定并比较三组大鼠心梗区域缺氧诱导因子(HIF)及血管内皮生长因子(VEGF)的表达情况及HE染色观察微血管再生情况。结果 EPO治疗组大鼠心功能较心肌梗死对照组大鼠明显改善,表现为LVDP值较心肌梗死对照组大鼠升高,但比假手术对照组低(P<0.01);EPO治疗组VEGF光密度为(195.8±3.6),明显高于假手术对照组光密度(165.6±1.8)和心肌梗死对照组光密度(172.8±2.5)(P<0.01);而心肌梗死对照组HIF-1光密度为(180.6±2.4),明显高于假手术对照组(172.6±2.3)和EPO治疗组(173.4±2.4)(P<0.01)。血管密度的检测发现梗死区EPO治疗组的血管密度(6.7±1.6)/视野高于心肌梗死对照组(4.9±1.2)/视野(P<0.05)。结论 EPO可以通过上调VEGF的表达来促进血管新生,改善心肌缺血缺氧状况,从而使HIF表达下降,并由此改善心功能。

Objective To evaluate the effects of erythropoietin on angiogenesis in rats with chronic myocardial infarction. Methods 30 male SD rats were divided into three groups, including sham operation group, myocardial infarction group and EPO treatment group,, respectively. Myocardial infarction models were created by ligating the left anterior descending coronary artery. The EPO treatment group was treated with daily intraperitoneal injection of rh - EPO （ 1000IU kg-1 ） , while the other two groups were given equivalent normal saline. 30 days after operation, the expression of Hypoxia - inducible factor 1 （ HIF - 1 ） and Vascular Endothelial Growth Factor （VEGF） were detected by immunohistochemieal method, and the angiogenesis was observed by HE staining. Meanwhile the cardiac function was assessed. Results The left ventricular developed pressure（LVDP） of EPO treatment group（ 82, 6 ± 8.2） was higher than the myocardial infarction group （ P〈 0. 01 ）, but lower than the sham operation group. The optical density of VEGF in EPO treatment group（ 195. 8 ±3.5） was significantly higher than those in the myocardial infarction group（ 172. 8 ±2.5） （ P〈 0. 01 ）and the sham operation group（ 165.6 ±- 1.8） （P 〈 0. 01 ） . The optical density of HIF- 1 in myocardial infarction group （180. 6 ± 2.4）was obviously higher than those in EPO treatment group （ 173.4 ± 2. 4） （ P 〈 0. 01 ） and sham operation group （ 172. 6 ± 2. 3 ） （ P 〈 0. 01 ）. The vascular density in EPO group （6. 7 ± 1.6 ）/visual field was higher than that in myocardial infarction group （4. 9 ± 1.2 ） / visual field （ P 〈 0. 05 ）. Conclusion Erythropoietin can improve heart function of rats with chronic myocardial infarction by upgrading the expression of VEGF, so as to improve the anoxic condition of ischemic myocardium and suppress the expression of HIF.