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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 investigate the regulatory effect of erythropoietin on microvascular regeneration in rats with chronic myocardial infarction (MI). Methods Thirty male SD rats were randomly divided into sham-operation control group, myocardial infarction control group and EPO-treated group. Myocardial infarction control group and EPO treatment group were established myocardial infarction model by ligation of left anterior descending coronary artery. The EPO group received daily intraperitoneal injection of EPO (1000 IU.kg-1), and the other two groups were injected with the same amount of saline. At 30 days after operation, the cardiac function of the rats in each group was measured. The expressions of hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF) and the expression of vascular endothelial growth factor (VEGF) were detected by immunohistochemistry and HE staining Observation of microvascular regeneration. Results Compared with the sham-operation control group, the EPO-treated rats had better cardiac function than those of the myocardial infarction control group. The LVDP values of the rats in the EPO-treated group were significantly higher than those in the control group (P <0.01) (195.8 ± 3.6), which was significantly higher than that of the sham operation control group (165.6 ± 1.8) and the myocardial infarction control group (172.8 ± 2.5) (P <0.01). However, the myocardial optical density of HIF-1 in the control group (180.6 ± 2.4), which was significantly higher than that of the sham-operation control group (172.6 ± 2.3) and EPO-treated group (173.4 ± 2.4) (P <0.01). The density of blood vessels in the EPO group was higher than that of the myocardial infarction group (6.7 ± 1.6) / field of vision (4.9 ± 1.2) / field of vision (P <0.05). Conclusion EPO can promote angiogenesis by up-regulating the expression of VEGF and improve the hypoxic-ischemic condition of myocardium, thus decreasing the expression of HIF and improving the cardiac function.